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PubMed1989

Tar content of cigarettes in relation to lung cancer.

Although it is generally considered established that the risk of lung cancer is directly related to the tar content of cigarettes, an examination of the results of previous studies does not yield conclusive evidence in favor of the hypothesis. The authors evaluated this issue in a study of 881 cases of lung cancer and 2,570 hospital controls who were 40 to 69 years of age; data were collected by interview in hospitals in the United States and Canada from November 1981 to June 1986. For each year of smoking, cigarette brands were classified according to their tar content as published in regular Federal Trade Commission reports (from 1967 to 1985) or the Reader's Digest (from 1957 to 1966). Tar values for years for which there was no published information were estimated by interpolation. Smokers were divided, according to the tar content of their cigarette brands averaged over a specified period, into low (less than 22 mg/cigarette), medium (22-28 mg/cigarette), and high (greater than or equal to 29 mg/cigarette) tar smokers. When the average tar content was based on cigarettes smoked at least 10 years previously, the relative risk estimates for medium and high tar smokers compared with low tar smokers were 3.0 and 4.0 after control for potentially confounding factors, including the number of cigarettes smoked per day. The trend was significant (p = 0.002). The tendency for the risk of lung cancer to increase with increasing tar content was consistent among men and women. The results provide further support for the hypothesis that the tar content of cigarettes is directly related to lung cancer risk. However, the data were limited in that there were very few subjects whose lifetime tar exposure averaged less than 10 mg/cigarette.

Adult↗
PubMed1992

Do smokers of lower tar cigarettes consume lower amounts of smoke components? Results from the Scottish Heart Health Study.

Data on 1133 men and 1621 women who smoke solely cigarettes with a known tar yield are extracted from the baseline population survey of the Scottish Heart Health Study. The expired-air carbon monoxide (CO-E), serum thiocyanate and serum cotinine values are compared between smokers in three tar groups: low (below 13 mg/cig.), middle (14-15 mg/cig.) and high tar (above 15 mg/cig.). An index of tar consumption is calculated assuming that the intake of different smoke components relative to one another is in proportion to their concentration in the smoke. CO-E and cotinine are found to peak in the middle tar group. Thiocyanate only tends to increase from low to middle tar group for women and from middle to high tar group for men. Tar consumption increases with tar yield of the cigarette smoked, but the increase is much lower than would be expected. We conclude that the tar yield of a cigarette is not an accurate guide to the amount of smoke components consumed by its smoker. Health professionals should be aware of these limitations of tar yield as a measure of cigarette strength.

Attitude to Health↗
PubMed1995

Cigarette smoking, tar yields, and non-fatal myocardial infarction: 14,000 cases and 32,000 controls in the United Kingdom. The International Studies of Infarct Survival (ISIS) Collaborators.

OBJECTIVES: To assess the effects of cigarette smoking on the incidence of non-fatal myocardial infarction, and to compare tar in different types of manufactured cigarettes. METHODS: In the early 1990s responses to a postal questionnaire were obtained from 13,926 survivors of myocardial infarction (cases) recently discharged from hospitals in the United Kingdom and 32,389 of their relatives (controls). Blood had been obtained from cases soon after admission for the index myocardial infarction and was also sought from the controls. 4923 cases and 6880 controls were current smokers of manufactured cigarettes with known tar yields. Almost all tar yields were 7-9 or 12-15 mg/cigarette (mean 7.5 mg for low tar (< 10 mg) and 13.3 for medium tar (> or = 10 mg). The cited risk ratios were standardised for age and sex and compared myocardial infarction rates in current cigarette smokers with those in non-smokers who had not smoked cigarettes regularly in the past 10 years. RESULTS: At ages 30-49 the rates of myocardial infarction in smokers were about five times those in non-smokers (as defined); at ages 50-59 they were three times those in non-smokers, and even at ages 60-79 they were twice as great as in non-smokers (risk ratio 6.3, 4.7, 3.1, 2.5, and 1.9 at 30-39, 40-49, 50-59, 60-69, 70-79 respectively; each 2P < 0.00001). After standardisation for age, sex, and amount smoked, the rate of non-fatal myocardial infarction was 10.4% (SD 5.4) higher in medium tar than in low tar cigarette smokers (2P = 0.06). This percentage was not significantly greater at ages 30-59 (16.6% (7.1)) than at 60-79 (1.0% (8.5)). In both age ranges the difference in risk between cigarette smokers and non-smokers was much larger than the difference between one type of cigarette and another (risk ratio 3.39 and 3.95 at ages 30-59 for smokers of similar numbers of low and of medium tar cigarettes, and risk ratio 2.35 and 2.37 at ages 60-79). Most possible confounding factors that could be tested for were similar in low and medium tar users, with no significant differences in blood lipid or albumin concentrations. CONCLUSION: The present study indicates that the imminent change of tar yields in the European Union to comply with an upper limit of 12 mg/cigarette will not increase (and may somewhat decrease) the incidence of myocardial infarction, unless they indirectly help perpetuate tobacco use. Even low tar cigarettes still greatly increase rates of myocardial infarction, however, especially among people in their 30s, 40s, and 50s, and far more risk is avoided by not smoking than by changing from one type of cigarette to another.

Adult↗
PubMed1986

Phlegm production and lung function among cigarette smokers changing tar groups during the 1970s.

In 1971-3 data on smoking habits, cigarette brand smoked, morning phlegm production, and lung function were recorded for factory workers as part of the Heart Disease Prevention Project. These men were reassessed in 1984 and those who had always smoked cigarettes from the same tar group were compared with those who had dropped one tar group (mean decreases of 6.6 mg tar, 0.1 mg nicotine) and two tar groups (mean decreases of 11.9 mg tar, 0.5 mg nicotine). Over the 13 years, men who had dropped one tar group were significantly more likely (p less than 0.05) to stop producing phlegm, but the effect was less marked for those who had dropped two tar groups. The mean fall in FEV1 was similar in all three groups, but 95% confidence limits showed that although dropping one tar group could be associated with at most a saving of 84 ml over the follow up period, there could be little extra benefit from dropping two tar groups. In 1984, all three groups of smokers excreted similar amounts of nicotine metabolites in the urine, suggesting that men who had dropped two tar groups compensated for the reduced nicotine yield of their cigarettes. This could account for the lack of a dose response relationship between reduction in the tar yield of cigarettes and cessation of phlegm and fall in FEV1.

Follow-Up Studies↗
PubMed1991

[Cell kinetic effects of crude coal tar application plus long wave ultraviolet radiation on normal and hyperproliferative epidermis of guinea pig skin].

This study investigated the cell kinetic effects of combined treatment with crude coal tar and long wave ultraviolet (UVA) radiation on the normal and n-hexadecane-induced hyperproliferative epidermis of guinea pig skin. Flow cytometry was used to determine the proportion of cells in S phase (S fraction) and G2 + M phase (G2 + M fraction). Bromodeoxyuridine incorporation was used to determine the labeling index. Conventional histologic techniques were used to observe the mitotic index. In the normal epidermis after a single treatment with tar and UVA (1 J/cm2) or tar alone, the labeling index showed an initial decrease of 4 hr duration followed by moderate increase. The initial decrease was more pronounced in the tar-UVA-treated epidermis than in the tar-treated epidermis. The mitotic index was depressed during the first 12 hr. S- and G2 + M fraction showed no changes during the first 12 to 18 hour, and then increased in varying degrees. In the hyperproliferative epidermis after two applications of tar and UVA (1 and 4J/cm2) or tar alone, the labeling index was depressed during the first 12 hr, and mitotic index was below the control level until the 36 hr. The inhibitory effects on DNA synthesis and mitosis were more pronounced in the tar-UVA-treated epidermis than in the tar-treated epidermis. The S- and G2 + M fraction exceeded the control level in varying degrees during the whole experimental period. The results indicate that tar inhibits the epidermal DNA synthesis and mitosis by itself, and that the inhibitory effects of tar are intensified by the radiation of UVA.

Alkanes↗
PubMed2001

DNA strand breaks, oxidative damage, and 1-OH pyrene in roofers with coal-tar pitch dust and/or asphalt fume exposure.

OBJECTIVE: To determine the potential for asphalt fume exposure to increase DNA damage, we conducted a cross-sectional study of roofers involved in the application of roofing asphalt. METHODS: DNA strand breaks and the ratio of 8-hydroxydeoxyguanosine (8-OHdG) to 2-deoxyguanosine (dG) were measured in peripheral blood leukocytes of roofers. In addition, urinary excretion of 8-OHdG and 8-epi-prostaglandin F2alpha (8-epi-PGF) was also measured. The study population consisted of 26 roofers exposed to roofing asphalt and 15 construction workers not exposed to asphalt during the past 5 years. A subset of asphalt roofers (n = 19) was exposed to coal-tar pitch dust (coal tar) during removal of existing roofs prior to applying hot asphalt. Personal air monitoring was performed for one work-week to measure exposure to total particulates, benzene-soluble fraction of total particulates, and polycyclic aromatic compounds (PACs). Urinary 1-OH-pyrene levels were measured as an internal biomarker of PAC exposure. RESULTS: Full-shift breathing zone measurements for total particulates, benzene-solubles and PACs were significantly higher for coal-tar exposed workers than for roofers not exposed to coal tar. Similarly, urinary 1-OH-pyrene levels were higher in coal-tar exposed roofers than roofers not exposed to coal tar. Total particulates or benzene-soluble fractions were not associated with urinary 1-OH-pyrene, but PAC exposure was highly correlated with urinary 1-OH-pyrene. When stratified by 1-OH-pyrene excretion, DNA strand breaks increased in a dose-dependent manner, and leukocyte 8-OHdG/dG decreased in a dose-dependent manner. Significant changes in DNA damage appeared to be linked to PACs from coal-tar exposure, although asphalt fume alone was associated with a small but significant increase in urinary 1-OH-pyrene and DNA strand breaks. CONCLUSIONS: Results are consistent with previous reports that asphalt or coal-tar exposure can cause DNA damage. Urinary 8-epi-PGF remained relatively constant during the week for virtually all subjects, regardless of exposure indicating that neither asphalt nor coal-tar exposure induces an overt oxidative stress. A small, but statistically significant increase in 8OHdG was evident in end-of-week urine samples compared with start-of-week urine samples in roofers exposed to coal-tar. The increase in urinary 8OHdG coupled with the decrease in leukocyte 8-OHdG/dG, suggests that coal-tar exposure induces protective or repair mechanisms that result in reduced levels of steady-state oxidative-DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

Inhibition of human immunodeficiency virus type-1 by retroviral vectors expressing antisense-TAR.

The human immunodeficiency virus type-1 (HIV-1) Tat activation response (TAR) region is essential for Tat-mediated trans-activation of the HIV-1 long terminal repeat (LTR). The TAR element is present on the 5' and 3' ends of all HIV-1 transcripts and is relatively conserved among different HIV-1 isolates. These properties make it an attractive target for anti-HIV-1 gene therapy strategies. We have constructed a Moloney murine leukemia-based retroviral vector that expresses a chimeric tRNA(iMet)-antisense TAR fusion transcript complementary to the HIV-1 TAR region. The potential of this anti-TAR retroviral vector to inhibit HIV-1 was initially tested by transient transfections with an HIV-1-LTR-Tat expression plasmid into HeLa-CAT cells. Anti-TAR inhibited Tat-mediated HIV-1 LTR-driven CAT reporter gene expression in a dose-dependent fashion. The antisense-TAR vector was then used to transduce the human SupT1 T cell line. Cotransfection of these SupT1 cells with a Tat expression plasmid plus an HIV-1 LTR-CAT reporter plasmid resulted in decreased CAT gene expression in comparison to control transduced SupT1 cells. The antisense-TAR engineered SupT1 cell line was then challenged with HIV-1MN.HIV-1 viral production was inhibited in SupT1 cells transduced with the antisense-TAR retroviral vector. Greater inhibition of HIV-1 was observed with antisense-TAR as compared to antisense-Tat expressing retroviral vector. These observations suggest that antisense-TAR retroviral vectors are potentially useful for clinical anti-HIV-1 gene therapy.

Blotting, Southern↗
PubMed1996

A small circular TAR RNA decoy specifically inhibits Tat-activated HIV-1 transcription.

Linear TAR RNA has previously been used as a decoy to inhibit HIV-1 transcription in vitro and HIV-1 replication in vivo. A 48 nucleotide circular RNA containing the stem, bulge and loop of the HIV-1 TAR element was synthesized using the self-splicing activity of a group I permuted intron-exon and was tested for its ability to function as a TAR decoy in vitro. This small circular TAR molecule was exceptionally stable in HeLa nuclear extracts, whereas a similar linear TAR molecule was rapidly degraded. The TAR circle bound specifically to Tfr38, a peptide containing the TAR-binding region of Tat. The ability of Tat to trans-activate transcription from the HIV-1 promoter in vitro was efficiently inhibited by circular TAR RNA but not by TAR circles that contained either bulge or loop mutations. TAR circles did not inhibit transactivation exclusively by binding to Tat since this inhibition was not reversed by adding excess Tat to the transcription reaction. Together, these data suggest that TAR circles act as decoys that inhibit transactivation by binding to Tat and at least one cellular factor. These data also demonstrate the utility of small circular RNA molecules as tools for biochemical studies.

Exons↗
PubMed1988

Maltose chemoreceptor of Escherichia coli: interaction of maltose-binding protein and the tar signal transducer.

The maltose chemoreceptor in Escherichia coli consists of the periplasmic maltose-binding protein (MBP) and the Tar signal transducer, which is localized in the cytoplasmic membrane. We previously isolated strains containing malE mutations that cause specific defects in the chemotactic function of MBP. Four of these mutations have now been characterized by DNA sequence analysis. Two of them replace threonine at residue 53 of MBP with isoleucine (MBP-TI53), one replaces an aspartate at residue 55 with asparagine (MBP-DN55), and the fourth replaces threonine at residue 345 with isoleucine (MBP-TI345). The chemotactic defects of MBP-TI53 and MBP-DN55, but not of MBP-TI345, are suppressed by mutations in the tar gene. Of the tar mutations, the most effective suppressor (isolated independently three times) replaces Arg-73 of Tar with tryptophan. Two other tar mutations that disrupt the aspartate chemoreceptor function of Tar also suppress the maltose taxis defects associated with MBP-TI53 and MBP-DN55. One of these mutations introduces glutamine at residue 73 of Tar, the other replaces arginine at residue 69 of Tar with cysteine. These results suggest that regions of MBP that include residues 53 to 55 and residue 345 are important for the interaction with Tar. In turn, arginines at residues 69 and 73 of Tar must be involved in the recognition of maltose-bound MBP and/or in the production of the attractant signal generated by Tar in response to maltose-bound MBP.

ATP-Binding Cassette Transporters↗
PubMed1991

Synthetic HIV-1 Tat can dissociate HeLa nuclear protein-TAR RNA complexes in vitro: a novel Tat-nuclear protein interaction.

Multiple binding of Tat and nuclear protein(s) to HIV-1 TAR RNA appears to be essential for the Tat-mediated trans-activation. As synthetic Tat-(1-47), which lacks the basic domain and does not bind TAR RNA in vitro, efficiently transactivated HIV-1 LTR in HeLa nuclear extracts, we hypothesized that Tat might trans-activate by interaction with TAR RNA via a host nuclear protein. The role of nuclear proteins in Tat-TAR interaction was examined through evaluation of several synthetic Tat peptides for ability to bind TAR RNA in vitro both in the presence and in the absence of HeLa nuclear proteins. Our data show that both Tat-(1-47) and Tat-(1-86) interact with TAR RNA-bound nuclear proteins, leading to dissociation of the nuclear protein-TAR RNA complexes; the N-terminal sequence of Tat appears to be involved in this interaction. Thus, after binding to TAR RNA, Tat can interact with a proximal TAR-bound nuclear protein and the resulting Tat-nuclear protein complex, now displaced from TAR, may initiate a facile and rapid assembly of the RNA polymerase II transcription complex. This study thus recognizes a novel interaction between Tat and a nuclear protein(s). Here we propose that the interaction of Tat with a nuclear protein(s) occurring on TAR RNA may be one of several steps in the mechanism of Tat-mediated trans-activation of the HIV-1 LTR.

Base Sequence↗
PubMed2001

Is compulsory restriction of tar yield of cigarettes a worthwhile public health policy?

BACKGROUND: Although the notion of a "safe cigarette" has proved an illusion, while people continue to smoke, an issue remains of whether compulsory restriction of tar yield is a worthwhile public health policy. METHODS: The study group was comprised of a random population sample of middle-aged Scottish men and women-3464 smokers of cigarettes with known tar yield at baseline. Tar yields were classified into low (< 10 mg), low/middle (10-14.99 mg), and middle or high (> or = 15 mg), according to standard groupings. Deaths within the study cohort were recorded over a period of 13 years. RESULTS: Among low, low/middle, and middle or high tar smokers, 55 (10%), 178 (16%), and 276 (16%), respectively, died. In a comparison group of lifetime never-smokers, 178 (6%) died. After adjustment for daily cigarette dose, duration of smoking, age, gender, social class, type A personality, body mass index, urinary potassium, and antioxidant vitamin consumption, hazard ratios (95% confidence intervals) for all-cause mortality comparing low-tar smokers to low/middle-tar smokers and to middle- or high-tar smokers were 1.64 (1.04-2.58) and 1.46 (0.95-2.26), respectively. Corresponding results for cardiovascular disease were 1.48 (0.74-2.96) and 1.35 (0.79-2.60). For lung cancer, after adjusting for known confounding factors, corresponding hazard ratios were 2.82 (0.98-8.15) and 2.30 (0.81-6.49). CONCLUSIONS: Smoking any type of cigarette is far more risky than abstaining altogether. Although the results obtained comparing tar levels are limited because of lack of repeat measures of smoking during follow-up, potential residual confounding factors, statistical imprecision, and failure to show a dose-response relationship, results do support the hypothesis that persistent smokers will reduce their tobacco-induced health risk if they smoke cigarettes with < 10 mg of tar. However, the data do not permit quantification of the benefits of switching to lower-tar cigarettes. Worldwide legislation to limit tar levels to 10 mg as an absolute maximum is recommended, while recognizing that this must be part of an integrated approach to tobacco control.

Adult↗
PubMed2003

Observer-blind, randomized, intrapatient comparison of a novel 1% coal tar preparation (Exorex) and calcipotriol cream in the treatment of plaque type psoriasis.

BACKGROUND: In a recent pilot study a novel, patented fatty acid-based 1% coal tar preparation (Exorex) has been found to be similar in efficacy to calcipotriol in the treatment of psoriasis. OBJECTIVES: Our aim was to investigate the therapeutic efficacy, safety and cosmetic acceptability of the new 1% coal tar preparation in comparison with calcipotriol cream in a larger patient cohort. PATIENTS AND METHODS: Forty patients with chronic plaque type psoriasis were included in this randomized, observer-blind, intrapatient comparison trial. In each patient two comparable target plaques were treated twice daily with 1% coal tar preparation or calcipotriol cream. At the onset of therapy and at weeks 2, 4, 6 and 8, the response to treatment was determined by the psoriasis severity index (PSI) that assesses the degree of erythema, infiltration and scaling of the psoriatic lesions on a five-point scale. In addition, all treatment-related side-effects were recorded and cosmetic acceptability of both treatments was rated every second week by the patients. After complete or near complete clearing the patients were followed up until relapse or for a maximum period of 18 months. RESULTS: Thirty-eight patients completed the study. At termination of the trial the mean +/- SD baseline PSI score of 9.2 +/- 1.5 was reduced to 3.0 +/- 2.9 by 1% coal tar preparation and to 2.8 +/- 2.7 by calcipotriol. The mean PSI reduction between baseline and final assessment did not differ significantly between 1% coal tar preparation and calcipotriol (P = 0.77). The mean intraindividual difference in reduction of PSI score between 1% coal tar preparation and calcipotriol was 0.1 score points (95% confidence interval - 0.84 to + 0.63). No difference between either preparation was observed with regard to time until relapse. Itching was caused by 1% coal tar preparation in four patients and by calcipotriol in one patient. Unpleasant odour or staining of the 1% coal tar preparation was reported by six patients, whereas one patient complained about the smell of the calcipotriol cream. CONCLUSIONS: The novel 1% coal tar preparation was found to be comparably as effective as calcipotriol in treating psoriasis. Tolerability and cosmetic acceptability was better for calcipotriol. Taking into consideration that the coal tar preparation is considerably less expensive than calcipotriol this new product appears as a very useful topical medication for chronic plaque type psoriasis.

Adult↗
PubMed1993

Covalent binding of polycyclic aromatic hydrocarbon components of coal tar to DNA in mouse skin.

Treatment of mouse skin with coal tar is known to initiate tumour formation, with the carcinogenic activity associated mainly with polycyclic aromatic hydrocarbons (PAHs). A sample of pharmaceutical coal tar was analysed by gas chromatography and 19 major PAHs were identified. 32P-postlabelling analysis was used to characterize those PAHs that are responsible for the DNA binding of coal tar and, by inference, its biological activity. PAHs were grouped according to their reported carcinogenic activities and applied as mixtures to mouse skin. Group A contained all of the 19 PAHs, group B seven PAHs for which there is sufficient evidence for carcinogenicity and group C 12 PAHs with only limited or inadequate evidence of carcinogenicity in experimental animals. 32P-Labelled DNA adducts formed by coal tar were resolved on TLC into a pattern of three discrete spots (2, 4 and 6) and four areas of diffuse radioactivity (1, 3, 5 and 7). By comparison of the pattern of adducts formed by coal tar with those formed by the synthetic mixtures it appeared that PAHs in group B formed coal tar-DNA adduct spots 4 and 6, and that adduct spot 2 was formed by PAHs in group C. Attempts to identify those PAHs responsible for the formation of coal tar-DNA adducts 4 and 6 were made by comparing the chromatographic mobilities of 32P-labelled coal tar-derived DNA adducts formed in mouse skin, using TLC and HPLC, with those formed by PAHs in group B. As benzo[ghi]perylene (B[ghi]P), a component of group C, has been demonstrated to exhibit significant DNA binding ability previously, the chromatographic mobility of coal tar-DNA adduct spot 2 was compared to that of the major DNA adducts formed by B[ghi]P in vivo and in vitro. It appeared that coal tar adduct spot 2 was the major adduct formed by B[ghi]P in vitro and that benzo[a]pyrene, benzo[b]fluoranthene, benzo [j]fluoranthene and benzo[k]fluoranthene contributed to the formation of adduct spot 6. None of the PAHs examined appeared to be responsible for the formation of adduct spot 4.

Animals↗
PubMed1995

The antifungal activity of a coal tar gel on Malassezia furfur in vitro.

OBJECTIVE: Seborrhoeic dermatitis is associated with Malassezia furfur, but the exact role of this lipophilic yeast is still unclear. The in vitro antifungal activity of a coal tar gel, the base of the gel and coal tar (Stantar) itself has been evaluated against 54 different M. furfur strains, isolated from patients suffering from dandruff, seborrhoeic dermatitis and pityriasis versicolor. METHODS: Minimum inhibitory concentrations (MICs) of the tested agents were measured by the agar dilution technique. RESULTS: The coal tar gel was found to be able to inhibit growth of 52 out of 54 investigated M. furfur isolates in vitro at MIC values between 625 and 10,000 micrograms/ml-corresponding to 3-5 micrograms/ml coal tar. However, the gel base also appears to be a less potent inhibitor of in vitro growth of M. furfur. In addition, it could be demonstrated that coal tar alone has an antifungal potential on M. furfur in vitro. MIC values from 250 to 5,000 micrograms/ml for coal tar were found. Presumably, both coal tar as the active ingredient and the gel base contribute to the in vitro activity of the coal tar gel against M. furfur. CONCLUSIONS: It is suggested that the effect of coal tar gel ointment in dandruff and seborrhoeic dermatitis therapy in vivo may be at least partly due to an antifungal activity of the coal tar but also of the gel base.

Antifungal Agents↗
PubMed2000

DNA adduct measurements, cell proliferation and tumor mutation induction in relation to tumor formation in B6C3F1 mice fed coal tar or benzo[a]pyrene.

Coal tar is a complex mixture containing hundreds of compounds, at least 30 of which are polycyclic aromatic hydrocarbons, including the carcinogen benzo[a]pyrene (BaP). Although humans are exposed to complex mixtures on a daily basis, the synergistic or individual effects of components within a mixture on the carcinogenic process remain unclear. We have compared DNA adduct formation and cell proliferation in mice fed coal tar or BaP for 4 weeks with tumor formation in a 2 year chronic feeding study. Additionally, we have analyzed tumor DNA for mutations in the K-ras, H-ras and p53 genes. In the forestomach of mice fed either coal tar or BaP an adduct indicative of BaP was detected, with adduct levels increasing in a dose-responsive manner. K-ras mutations were detected in the forestomach tumors, with the incidence being similar in mice fed coal tar or BaP. These results suggest that the BaP within coal tar is associated with forestomach tumor induction in coal tar-fed mice. DNA adduct levels in the small intestine were not predictive of tumor incidence in this tissue; instead, the tumors appeared to result from compound-induced cell proliferation at high doses of coal tar. K-ras mutations were detected in lung tumors. Since lung tumors were not increased by BaP, coal tar components other than BaP appear to be responsible for the tumors induced in this tissue. H-ras mutations, primarily occurring at codon 61, were the most common mutation observed in liver tumors induced by coal tar. Since this mutation profile is observed in spontaneous hepatic tumors, components in the coal tar may be promoting the expansion of pre-existing lesions.

Animals↗
PubMed1993

TARS. Their role in the treatment of psoriasis.

The clinical experience reported by these studies does not definitively answer the question of whether or not all or even most tars are effective in the treatment of psoriasis. Information supports both views. With the present data, the following statements seem appropriate: 1. Tar alone may be helpful for a subset of individuals with mild to moderate psoriasis. Because the majority of patients with psoriasis have less than severe disease, this group numerically represents the majority of office-treated patients. For these patients, tars are not unreasonable to use in appropriate clinical circumstances. 2. Crude coal tar is not likely more beneficial than modified tar or gels. These latter preparations have much better patient acceptance and compliance because of decreased odor, staining, and messiness. 3. Overall, the potential severity of side effects from tars is less than that from anthralin and much less than that from topical corticosteroids (atrophy, rebound). 4. Clinical experience confirms that tar preparations can be effective when other modalities fail or cannot be used for reasons of adverse effects or otherwise. 5. Tar shampoos are considered useful therapeutic agents for active clearing therapy and for maintenance. 6. When combined with suberythemogenic ultraviolet light B, tar can be a useful agent. It has fewer side effects in terms of burning and irritation than does aggressive ultraviolet B therapy alone. The effect of maximal erythemogenic ultraviolet light B therapy is not enhanced with tar. Practically speaking, however, the majority of psoriatic patients do not require, or are not able to avail themselves of, convenient controlled ambulatory ultraviolet light therapy.

Dosage Forms↗
PubMed1991

Mapping of HIV-1 Tat protein sequences required for binding to Tar RNA.

We have utilized a gel retardation assay to study the binding of chemically synthesized domains of the HIV-1 Tat protein to radiolabeled trans-activating response element (Tar) RNA. As with recombinant Tat protein, synthetic Tat specifically binds to Tar RNA and not to a defective Tar RNA or to anti-sense Tar RNA. The 6 amino acid portion of the basic region containing five arginines is sufficient to confer Tar binding to overlapping Tat protein fragments; Tat fragments that lack the basic region do not bind Tar. In addition, the basic region alone can also bind Tar RNA; however, binding of the basic region is non specific since defective Tar RNA is bound as well as wild type Tar RNA. Binding specificity for wild type Tar RNA can be conferred by the addition of a minimum of 8 random amino acids to either end of the basic region.

Amino Acid Sequence↗
PubMed2003

Mg2+-induced variations in the conformation and dynamics of HIV-1 TAR RNA probed using NMR residual dipolar couplings.

The effects of divalent Mg(2+) on the conformation and dynamics of the stem-loop transactivation response element (TAR) RNA from HIV-1 have been characterized using NMR residual dipolar couplings (RDCs). Order matrix analysis of one bond 13C-1H RDCs measured in TAR at [Mg(2+)]:[TAR] stoichiometric ratios of approximately 3:1 (TAR(3.0Mg)) and approximately 4.5:1 (TAR(4.5Mg)) revealed that Mg(2+) reduces the average inter-helical angle from 47(+/-5) degrees in TAR(free) to 5(+/-7) degrees in TAR(4.5Mg). In contrast to the TAR(free) state, the generalized degree of order for the two stems in TAR(4.5Mg) is found to be identical within experimental uncertainty, indicating that binding of Mg(2+) leads to an arrest of inter-helical motions in TAR(free). Results demonstrate that RDC-NMR methodology can provide new insight into the effects of Mg(2+) on both the conformation and dynamics of RNA.

HIV Long Terminal Repeat↗