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Evidence for a base triple in the free HIV-1 TAR RNA.

We propose the existence of a novel base triple in the HIV-1 TAR hairpin. This triple is supported by covariation of loop residue 31 with residue 22, which is part of an unusual base pair with U40 below the 3-nucleotide bulge. A set of mutants was constructed to test the involvement of bases A22, U31, and U40 in a triple interaction. RNA structure probing, trans-activation assays, and structure modeling are consistent with the existence of this base triple in a bent conformation of the free TAR element. However, disruption of the base triple does not affect binding of a Tat-derived peptide. We therefore compared the structure of free and Tat-bound TAR RNA by footprinting and site-specific cross-linking analyses. These studies indicate that the Tat arginine-rich motif, in addition to its known binding site at the bulge, is in close contact with U31 in the TAR loop. Because binding of Tat to TAR is known to coincide with the formation of a base triple with residues U23, A27, and U38, we hypothesize that Tat binding and the associated straightening of TAR triggers the disruption of the (A22-U40)U31 triple.

Gene Products, tat↗

Family physicians and youth tobacco-free education: outcomes of the Colorado Tar Wars program.

BACKGROUND: Tar Wars is a national school-based tobacco-free education program operated by the American Academy of Family Physicians. The Tar Wars lesson uses an interactive 45-min session taught by volunteer family physicians in 4th- and 5th-grade classrooms and focuses on the short-term image-based consequences of tobacco use. In this study, we evaluated the effectiveness of the Tar Wars program in Colorado with both quantitative and qualitative measures. METHODS: Students participating in the quantitative evaluation were tested before and after a Tar Wars teaching session using a 14-question test covering the short-term and image-based consequences of tobacco use, cost of smoking, tobacco advertising, and social norms of tobacco use. Qualitative evaluation of the program included guided telephone interviews and focus groups with participating students, teachers, and presenters. RESULTS: Quantitative evaluation showed statistically significant improvement in correct responses for the 14 questions measured with an average increase in correct responses from 8.95 to 10.23. Three areas recommended by the Centers for Disease Control (CDC) for youth tobacco prevention showed greater change in correct responses, including cost of smoking, truth of tobacco advertising, and peer norms of tobacco use. Qualitative evaluation found that the overall message of the session was well received, that previously known tobacco information was reinforced by its presentation in a novel format, and that new information learned included cost of smoking, truth of tobacco advertising, and peer norms of tobacco use. CONCLUSIONS: The Tar Wars lesson plan is effective in increasing students' understanding about the short-term consequences of tobacco use, cost of tobacco use, truth of tobacco advertising, and peer norms. Tar Wars meets the CDC guidelines as one component of effective comprehensive youth tobacco prevention.

Child↗

Cumulative tar exposure. A new index for estimating lung cancer risk among cigarette smokers.

A new index for estimating lifetime exposure to tar from cigarette smoking was found to be the best measure of the relative risk for Kreyberg type I (KI) and Kreyberg type II (KII) lung cancer in a case-control study of 2296 cases (1274 KI and 1022 KII) and 4667 controls. There is a steep, near-linear dose-response of lung cancer risk of both histologic types to cumulative exposure to tar, although the odds ratios are three to five times higher for KI than for KII. The odds ratios for lung cancer in women are consistently higher than those in men with the same level of exposure to tar, particularly among long-term smokers who smoke heavily. Based on their estimates of odds ratios associated with tar exposure, the authors projected an approximate 15-20% decrease in KI lung cancer risk among long-term smokers who smoked heavily for every 10-mg decrease in tar in the cigarettes they smoked.

Age Factors↗

Comparative carcinogenic and mutagenic activity of coal tar and petroleum asphalt paints used in potable water supply systems.

Coal tar and petroleum asphalt paints are among the products used as coatings for water pipes and storage tanks to retard corrosion. Formulations of these coatings were tested in the Ames mutagenesis and the mouse skin carcinogenesis bioassays. To test the mutagenicity of the paints, six doses ranging from 0.005 to 10 microliters per plate were assayed. In the mouse skin bioassay, doses of the coal tar paints ranging from 0.2 to 200 microliters were administered topically to 30 SENCAR mice per group. These initiating doses were followed by applications of 1.0 micrograms of 12-o-tetradecanoyl-phorbol-13-acetate (TPA) in 0.2 ml acetone topically, three times weekly for 20 weeks. Petroleum asphalt paints were tested in groups of 40 animals at 200 and 600 microliters doses. All coal tar paints showed mutagenic activity after metabolic activation with S-9, with the highest response being in strains TA 98 and TA 100. None of the petroleum asphalt paints gave mutagenic responses. Both types of coatings resulted in positive responses in the initiation/promotion study. The coal tar paints gave rise to 1000-1800 times the tumor response observed with petroleum asphalt products. One coal tar product was positive when tested as a complete carcinogen in the mouse at 2 microliters per application once weekly for 30 weeks, whereas the asphalt paint was negative at 100 times the dose. The biological responses to the products were greater than expected from their polycyclic aromatic hydrocarbon (PAH) content. These findings suggest that the hazard posed by these coatings may not be fully explained by their PAH contents.

Animals↗

Management of tar and asphalt injuries.

Tar and asphalt burns are unique injuries because the chemical is difficult to remove without inflicting further tissue injury. Since 1978, 42 patients have been treated for hot tar or asphalt injuries, 30 of whom required hospitalization. Inpatients were all male with a mean age of 27.2 years and a mean burn size of 9.3 percent total body surface area (mean full-thickness injury 5.3 percent total body surface area). Burns of critical areas were present in 63.3 percent of the inpatients. A petroleum-based, surface-active solvent was used to remove the tar or asphalt. This solvent proved nonirritating and removed tar much faster than other agents. Early excisional therapy was performed in 63.4 percent of the patients, 80 percent of whom returned to work within 6 weeks of injury. Principles of management include rapid cooling of tar or asphalt to solidify the inciting agent and dissipate heat; removal with a new, non-toxic solvent; early excision and grafting of appropriate injuries; and an aggressive, early back-to-work philosophy.

Accidents, Occupational↗

Cigarette tar causes single-strand breaks in DNA.

The results of this study demonstrate, for the first time, that cigarette tar causes DNA damage. Incubation in vitro of phage PM2 DNA with aqueous extracts of cigarette tar results in the introduction of DNA single-strand breaks. The effects of protective enzymes and radical scavengers indicate the involvement of active oxygen species. Although the semiquinone components of tar reduce dioxygen forming superoxide radicals and hydrogen peroxide, our results suggest that hydroxyl radicals formed via metal catalyzed decomposition of hydrogen peroxide are ultimately responsible for the DNA lesions. Our results also suggest that the metals in tar are reduced by the semiquinone components of tar and by superoxide at comparable rates.

Bacteriophages↗

Exposure to carbon monoxide in smokers of middle- and low-tar cigarettes.

The carbon monoxide (CO) exposure of habitual middle-tar (MT) and low-tar (LT) smokers was studied in a group of 78 subjects (38 male and 40 female). CO intake from a single cigarette (measured by the rise in expired-air CO concentration) was significantly less in LT smokers. Longer term exposure, measured by pre-smoking CO levels, was also less in LT smokers, but not significantly so. A CO-based index showed that LT cigarettes were relatively more intensively smoked. Exposure to nicotine and tar was estimated by applying the index of smoking intensity to the standard nicotine and tar yields of the brands smoked. Although an indirect estimate, the results suggest that the intake of tar and nicotine is likely to be appreciably less in LT smokers than in their MT counterparts. The likely difference in intake, however, is not as great as the difference in smoking-machine yields.

Adult↗

Contribution of primary aromatic amines to the mutagenicity of gasifier tars and coal oils.

Two reactions that chemically alter primary aromatic amines (PAA) were used to assess the contribution of these compounds to the indirect bacterial mutagenicity of tar from an experimental low Btu gasifier. The first reaction, nitrosation, effectively eliminated the mutagenicity of several PAA standards and a coal oil when run in a low pH media (1.2). When applied to gasifier tar, extensive direct (not requiring metabolic activity) mutagenicity was generated. This direct mutagenicity limited the interpretation of results. When the pH of the reaction media was raised to 2.5, the mutagenicity of PAA standards and the coal oil were still greater than 90% eliminated, however, no direct mutagenicity was observed for the gasifier tar. Furthermore, only 61% of the indirect (requiring metabolic activation) mutagenicity was eliminated. Acetylation reduced the indirect activity of most primary amine standards by greater than 79%. Acetylation of the tar likewise eliminated part, but not all, of the activity, whereas most of the activity of the coal oil was eliminated. These results indicated that a much lower percentage of the mutagenic activity of low Btu coal tar samples was due to primary aromatic amines than was the case for coal oil.

Acetylation↗

Carcinogenic effects in A/J mice of particulate of a coal tar paint used in potable water systems.

Coal tar paints are among the products used as inside coatings for water pipes and storage tanks to retard corrosion in potable water supply systems. Four different formulations of these paints were tested in earlier work by this laboratory in the Ames mutagenesis and the mouse skin carcinogenesis bioassays. The paint most active in these assays were then tested in a particulate form in the lung adenoma assay with A/J mice. The paint was applied to clean glass plates, cured, collected and homogenized in 2% Emulphor. Doses of this coal tar suspension were administered by gavage at 1.0, 10.0 and 55.0 mg in 0.2 ml per mouse 3X weekly for 8 weeks. The total doses of coal tar paint were 24, 240, and 1320 mg/mouse. Benzo[a]pyrene (BaP), administered in a parallel schedule to a total dose of 6 mg/mouse, served as positive control. A negative control group received an equivalent volume of 2% Emulphor. Animals were killed at 9 months of age (8 months after first dose) and lung adenomas counted. A dose-related response, in the average number of lung tumors per mouse, was observed with the coal tar particulate. There were also squamous cell tumors of the forestomach in 42% of the mice receiving 55.0 mg coal tar paint per application.

Animals↗

Urinary excretion of mutagens in smokers of cigarettes with various tar and nicotine yields, black tobacco, and cigars.

Frameshift mutagens were isolated and concentrated from smokers' urine employing a method recently described. Urine concentrates of the habitual smokers and non-smokers who smoked cigarettes with low-, medium-, and high tar/nicotine yields, RCN (Reduced Condensate and Nicotine; artificial cigarettes containing cotobacco materials), black tobacco, and cigars were tested for mutagenicity in the Salmonella/mammalian microsome assay using Salmonella typhimurium TA98. Non-smokers who smoked 5 and habitual smokers who smoked 10 cigarettes of various tar and nicotine yields excreted more mutagens in urine with low-tar cigarettes than with medium- or high-tar cigarettes. Consuming more than 10 cigarettes a day resulted in a higher urinary excretion of mutagens with medium-tar cigarettes than with high-tar cigarettes. Smoking 5 RCN cigarettes a day by habitual smokers resulted in a higher urinary excretion of mutagens than smoking 5 commercial brand of cigarettes. In contrast, smoking 10 RCN cigarettes resulted in a lower urinary excretion of mutagens than smoking 10 commercial brand of cigarettes. The highest mutagenic activity was found with the urine of a habitual black tobacco smoker. Smoking cigars by non-smokers resulted in a very weak mutagenic activity of urine.

Adult↗

Source diagnostic and weathering indicators of tar balls utilizing acyclic, polycyclic and S-heterocyclic components.

This study represents a forensic chemical analysis to define the liability for the coastal bitumens polluting the beaches of the Mediterranean city of Alexandria. Six tar balls collected from several locations along the coast of the city were analyzed for their acyclic and polycyclic hydrocarbons as well as sulfur heterocycles using GC/FID, GC/AED and gas chromatography/mass spectrometry techniques. The analysis of one Egyptian crude oil is also included as a possible source oil. The tar ball samples were at early stages of weathering. Based on the GC traces and biomarker signatures, the tar balls could be genetically different. One sample collected from the Eastern Harbor region appears to be a Bunker C type fuel produced from Egyptian crudes. The refining process has removed the low molecular weight components. On the other hand, the wide n-alkane distribution together with the absence of an unresolved complex mixture suggests that crude oils probably from tank washings, ballast discharges or accident spills from tankers could have contributed significantly to the other tar ball samples. The distribution of source specific hopane and sterane markers revealed that the tar samples probably originate from different oil fields.

Bathing Beaches↗

Bioremediation of coal tar PAH in soils using biodiesel.

The addition of biodiesel together with nitrate and phosphate to soil containing coal tar, in laboratory and field experiments, resulted in degradation of coal tar polycyclic aromatic hydrocarbons (PAH) that was not apparent when the nutrients alone were added. The addition of motor diesel fuel instead of biodiesel was also tested. Over the 55 days of the field and laboratory experiments, the biodiesel resulted in an increased degradation of naphthalene in the coal tar by 52% and 85%, respectively, and motor diesel resulted in increased depletions of 85% and 96%, respectively. Other PAH containing up to four rings were depleted to lesser extents. The increases in PAH biodegradation by the diesel treatments were ascribed to tar solubilisation and dispersion thereby increasing the PAH bioavailability. The ready biodegradability and low phytotoxicity of biodiesel suggest that it may be suitable as a novel treatment for the bioremediation of coal tar contaminated soils.

Biodegradation, Environmental↗

Incidence of skin cancers in patients with atopic dermatitis treated with coal tar. A 25-year follow-up study.

Coal tar ointments have been used for many years in the treatment of chronic eczematoid dermatitis. The possible carcinogenic effect of coal tar ointment and ultraviolet light (Goeckerman regimen), considered individually or in combination, has been of concern to physicians. A 25-year follow-up study was completed on 426 patients with atopic dermatitis and neurodermatitis who were hospitalized and treated with coal tar ointments and ultraviolet light at the Mayo Clinic from 1950 through 1954. These results were compared with those from a similar study that examined patients with psoriasis who also were treated with coal tar ointments and ultraviolet light. The results of this study suggest that the incidence of skin cancer is not significantly increased above the expected incidence for selected populations of the United States. This study offers reassurance about the relatively small risk of skin cancer developing in patients with atopic dermatitis and neurodermatitis treated with coal tar ointments and ultraviolet light (Goeckerman regimen).

Basal Cell Carcinoma↗

Psoriasis treatment with suberythemogenic ultraviolet B radiation and a coal tar extract.

Forty-nine patients with plaque-type psoriasis were enrolled in a randomized prospective trial that compared the efficacy of outpatient treatment with suberythemogenic doses of ultraviolet B (UVB) radiation administered with a tar oil to treatment with maximally erythemogenic UVB radiation with emollients. Seventeen percent of patients treated with tar oil and 26% of patients treated with maximally erythemogenic UVB failed to adhere to the protocol. Although the tar oil protocol seemed slightly less effective in those with more severe psoriasis, a roughly comparable fraction of patients who adhered to either protocol cleared at least 90% of psoriasis on surfaces exposed to UVB (76% vs 100%). The total dose of UVB to clearing was 44% less for patients treated with tar oil and suberythemogenic UVB. For most patients with moderate psoriasis, suberythemogenic UVB and tar oil is an effective, low-cost, and acceptable outpatient therapy.

Adult↗

Cigarette smoke-induced protein oxidation and proteolysis is exclusively caused by its tar phase: prevention by vitamin C.

We have reported before that whole phase cigarette smoke (CS) contains stable oxidants that cause oxidative damage and increased proteolysis of proteins [Free Radic. Biol. Med. 27 (1999) 1064]. Here, we demonstrate that these oxidants are exclusively present in the tar phase of the CS and not its gas phase and can almost wholly account for the observed whole phase CS-induced oxidation of human plasma proteins as well as extensive oxidative proteolysis of guinea pig lung and heart microsomal proteins in vitro. The mechanism of the tar phase CS-induced proteolysis of microsomal proteins involves two-steps: (i) initial oxidation of the proteins by oxidants present in the tar extract followed by (ii) rapid proteolytic degradation of the oxidized proteins by proteases present in the microsomes. Like the whole phase CS, the oxidative damage of proteins caused by the tar phase CS, as evidenced by the formation of protein carbonyl and bityrosine as well as loss of tryptophan residues and thiol groups, is also almost completely prevented by ascorbic acid and only partially by glutathione. Other antioxidants, including superoxide dismutase, catalase, vitamin E, beta-carotene and mannitol are ineffective. This again leads us to suggest that adequate intake of vitamin C may help smokers to evade the CS-induced degenerative diseases associated with oxidative damage. The revelation of the acute toxicity of the tar phase with respect to CS-induced oxidative damage also urges the necessity of trapping it more effectively by suitable cigarette filters to reduce the health damage caused to smokers.

Animals↗

[What perception have smokers of nicotine and tar yields of cigarettes?].

INTRODUCTION: Advertising information on cigarette package participate to the reduction of health risks from smoking. Impact on smokers has been poorly studied. This study intended to determine the smoker perception of nicotine and tar yields of cigarettes. METHODS: Consulting in an outpatient smoking cessation clinic, 171 smokers answered freely and spontaneously to a questionnaire evaluating their perception of nicotine and tar yields, cigarette consumption (number and brand), nicotine dependence. Simultaneously, biological tobacco markers were measured. RESULTS: The number of cigarettes, nicotine dependence and specific tobacco markers were not significantly different according to the cigarette type: "full savour", "light" or "ultra light". Women smoked less than men and 54% preferred "light" cigarettes versus 37% of men. These smokers were entering a tobacco cessation program, it was assumed they had lead a prior reflection about their smoking habits. Only 8% of them gave the correct values of nicotine and tar yields and 14% gave approximate values. Tar levels were highly underestimated. CONCLUSIONS: This study shows that smokers have actually no interest for nicotine and tar yields. As the new decree which modifies manufacture's obligation concerning the legal mentions, is applicable in January 2004 in France; our conclusion may change in the future.

Adult↗

A strong genotoxic effect in mouse skin of a single painting of coal tar in hairless mice and in MutaMouse.

The dorsal skin of C3H/Tif/hr hairless mice was painted with coal tar, pharmacological grade. Epidermal cells and hepatocytes were isolated after 4, 24, 48 and 96 h and DNA strand breaks were determined as tail moment by the alkaline comet assay. The tail moment of epidermal cells was significantly greater at the time points 4, 24, 48 and 96 h after exposure compared to the controls, with the most DNA strand breaks at 24 h. The DNA strand breaks in epidermal cells increased linearly with the dose of coal tar. In hepatocytes, no difference in DNA strand breaks was found between exposed animals and controls. DNA adducts were determined by the 32P-postlabeling assay. For epidermal cells, the mean DNA adduct level was 12-fold greater in coal tar painted mice after 24 h than in controls. Again, a linear dose/response relationship was seen 24 h after painting. For liver DNA, the mean DNA adduct level was 3-fold greater than for controls. The mutation frequency in epidermal and liver cells was examined in lambdalacZ transgenic mice (MutaMouse). Thirty-two days after painting, the mutation frequency in epidermal cells was 16-fold greater in coal tar treated mice compared to controls. No effect was detected in hepatocytes. We found that a single painting of coal tar resulted in strong genotoxic effects in the murine epidermis, evidenced by induction of DNA strand breaks and DNA adducts in hairless mice and lambdalacZ mutations in the MutaMouse. This demonstrates that it is possible to detect genotoxic effects of mixtures with high sensitivity in mouse skin by these end-points.

Administration, Cutaneous↗

PAHs and organic matter partitioning and mass transfer from coal tar particles to water.

The coal tar found in contaminated soils of former manufactured gas plants and coking plants acts as a long-term source of PAHs. Organic carbon and PAH transfer from coal tar particles to water was investigated with closed-looped laboratory column experiments run at various particle sizes and temperatures. Two models were derived. The first one represented the extraction process at equilibrium and was based on a linear partitioning of TOC and PAHs between coal tar and water. The partition coefficient was derived as well as the mass of extractable organic matter in the particles. The second model dealt with mass transfer. Particle diffusion was the limiting step; organic matter diffusivity in the coal tar was then computed in the different conditions. A good consistency was obtained between experimental and computed results. Hence, the modeling of PAH migration in contaminated soils at the field scale requires taking into account coal tar as the source-term for PAH release.

Coal Tar↗