Biomedical subjects

H Autrup

Publications and source records attributed to H Autrup.

At least 19 recordsLinked to original sources

PubMed1996

Comparative synchronous fluorescence spectrophotometry and 32P-postlabeling analysis of PAH-DNA adducts in human lung and the relationship to TP53 mutations.

Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were studied in human lung from 39 lung cancer patients by synchronous fluorescence spectrophotometric (SFS) and 32P-postlabeling assays. Regression analysis of the samples failed to detect any correlation between benzo[a]pyrene-diolepoxide (BPDE)-DNA adducts detected by SFS and the BPDE co-migrating spot detected by 32P-postlabeling. We have also analyzed the relationship between adduct levels and TP53 mutations. By postlabeling diagonal radioactive zone (DRZ) adducts were detected in 37 of 39 (95%) lung tissues from lung cancer patients and the adduct level ranged from 6.81 to 108.50 adducts/10(8) nucleotide. Thirty-three of 39 (85%) had detectable levels of BPDE-DNA adducts (> 1 adduct/10(9) nucleotide). Current heavy smokers (> 20 cigarettes/day) have significantly higher DRZ adduct levels compared to individuals smoking less than 20 cigarettes/day. By SFS combined with immunoaffinity column (IAC), 11 of 39 (28%) samples had detectable adduct levels, and 6 of 11 (55%) were detectable by SFS following purification of benzo[a]pyrene (BP)-tetrols by high pressure liquid chromatography (HPLC). Six of 33 (18%) samples were positive for BPDE-DNA adducts by both postlabeling and HPLC/SFS. No correlation was observed between the SFS and 32P-postlabeling assays for the detection of BPDE-DNA adducts. However, there was a good correlation between adduct levels detected by IAC/SFS and HPLC/SFS. We found a weak association between total PAH-DNA adduct levels in lung tissue and TP53 mutations.

Adult↗

PubMed1996

Biomonitoring of diesel exhaust-exposed workers. DNA and hemoglobin adducts and urinary 1-hydroxypyrene as markers of exposure.

Diesel exhaust-exposed workers have been shown to have an increased risk of lung cancer. A battery of biomarkers were evaluated for their ability to assess differences in exposure to genotoxic compounds in bus garage workers and mechanics and controls. Lymphocyte DNA adducts were analyzed using the 32P-postlabelling method with butanol and P1 enrichment procedures. Hydroxyethylvaline (HOEtVal) adducts in hemoglobin were measured by gas chromatography-mass spectrometry (GC-MS) and 1-hydroxypyrene (HPU) in urine determined using HPLC analysis. The exposed workers had significantly higher levels of all three biomarkers compared to the controls. Total DNA adduct levels were 0.84 fmol/micrograms DNA vs 0.26 in controls (butanol) and 0.65 fmol/micrograms DNA vs. 0.08 (P1 nuclease). Median HOEtVal adduct level in exposed workers was 33.3 pmol/g hemoglobin vs. 22.1 in controls. HOEtVal adducts correlated with HPU but not with DNA adducts. The levels of HPU in urine were 0.11 micromol/mol creatinine compared to 0.05 in controls. All three assays applied were sensitive enough to evaluate a low level of exposure to environmental pollutants, with postlabelling and GC-MS as the most sensitive assays. The study indicated that skin absorption of polycyclic aromatic hydrocarbons (PAH) might be an important factor to consider when studying PAH exposure from air pollution sources.

Adult↗

PubMed1996

Autoregulation of human CYP1A1 gene promotor activity in HepG2 and MCF-7 cells.

Cytochrome CYP1A1 gene expression, induced by polycyclic aromatic hydrocarbons and dioxins, eg. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is regulated mainly at the level of transcription. Inducible activation of the CYP1A1 promotor is mediated by a ligand-dependent transcription factor dimer complex including the aryl hydrocarbon receptor (AHR) and the AHR nuclear translocator (ARNT) proteins. Additional factors seem to be involved in tissue- and cell-specific modification of the induction process. In the present study HepG2 and MCF-7 cell lines were used to examine a possible cell-specific autoregulation of CYP1A1 promotor function. Chimeric CYP1A1-CAT reporter constructs and a human CYP1A1 cDNA expression plasmid were used in transient co-expression experiments. In HepG2 cells co-expression of increasing amounts of CYP1A1 cDNA significantly down-regulated constitutive as well as the TCDD-induced CYP1A1 promotor driven CAT activity. In contrast, co-transfection of MCF-7 cells with a 3-fold molar excess of CYP1A1 cDNA relative to the CYP1A1-CAT reporter construct caused an approximately 2-fold increase in the TCDD-induced CAT activity, whereas no effect was observed on constitutive promotor activity. This autoregulatory mechanism(s) of the human CYP1A1 gene product was independent of specific 5' flanking promotor segments tested. RT-PCR analyses did not indicate any changes in mRNA level of AHR and ARNT in the co-transfection studies. Thus these studies show that the human CYP1A1 gene is exposed to cell-specific autoregulation, probably achieved via different functions of trans-acting factors.

Aryl Hydrocarbon Receptor Nuclear Translocator↗

PubMed1996

Environmental air pollution and DNA adducts in Copenhagen bus drivers--effect of GSTM1 and NAT2 genotypes on adduct levels.

The lymphocyte bulky PAH-DNA adduct levels have been studied in persons occupationally exposed to ambient air pollution. The exposure group consisted of 90 healthy, nonsmoking bus drivers from the Copenhagen area, divided into three exposure groups according to driving area, and 60 rural controls (smokers and non-smokers). PAH-DNA adducts were determined by 32P-postlabelling with the butanol enrichment procedure. The bus drivers answered a comprehensive questionnaire on passive smoking, residential area, diet and other potential confounding variables. A significantly higher adduct level was observed in bus drivers working in central Copenhagen (1.214 fmol/microg DNA, n = 49) compared with both those driving in the dormitory (median: 0.507 fmol/microg DNA, P = 0.046, n = 16) and suburban (median: 0.585 fmol/microg DNA, P = 0.041, n = 25) areas. All three groups had higher adduct levels than rural controls (0.074 fmol/microg DNA, n = 60, P < 0.001). No significant influence on adduct levels was demonstrated from potential confounders, including smoking and diet. The effect of the metabolizing enzymes, GSTM1 and NAT2, on adduct levels was investigated. No statistically significant effects were observed on adduct levels from GSTM1 or NAT2, either individually or combined, but a non-significant trend was seen for individuals with GSTM1*0/0 (null), since they had higher adduct levels in all exposure groups. This study demonstrated that lymphocyte PAH-DNA adduct levels were related to levels of exposure to urban air pollution and indicated that these adducts might be helpful as a means of classifying better different exposure groups for epidemiological studies. Furthermore, it demonstrated the ability of 32P-postlabelling to discern small differences in low exposure to ambient air pollution and suggested a possible effect of GSTM1*0/0 on DNA adduct levels.

Adult↗

PubMed1996

Aflatoxin B1 induced lacI mutation in liver and kidney of transgenic mice C57BL/6N: effect of phorone.

Transgenic C57BL/6N mice containing a lambda shuttle vector carrying a lacI target and an alpha-lacZ reporter gene have been used to study the modulating effect of phorone, a glutathione-depleting agent, on the mutagenic activity of aflatoxin B1 (AFB1) in vivo. Animals were treated with AFB1 (8 mg/kg) for four consecutive days and the animals sacrificed 21 days after the last treatment. Treatment with AFB1 alone did not result in a significant increase in mutation frequency in the liver and kidney. When the animals were treated with phorone 4 h prior to treatment with AFB1 a significant increase in mutation frequency was observed in the liver (4-fold) and kidney (1.5-fold). Phorone treatment did not increase the AFB1-induced mutation frequency in the lung and intestine. DNA sequence analyses of 30 independent clones isolated from the liver of AFB1-treated animals showed that G:C --> T:A transversion (60%) was the predominant mutational event. Mutations within the lacI gene could not be detected in seven of 30 mutants. The mutations were randomly distributed throughout the coding sequences of the lacI gene and no hotspots for the mutations were observed. However, codons 86 and 928 appeared to be major sites for mutation. The study shows that the transgenic mouse in vivo mutagenesis model can be used to study the influence of effect-modifying compounds on the mutagenic activity of known carcinogens.

Aflatoxin B1↗

PubMed1996

Biomonitoring human exposure to environmental carcinogenic chemicals.

A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological effects (mutation and cytogenetic damage). Adduct detection at the level of DNA or protein (haemoglobin) was carried out by 32P-postlabelling, immunochemical, HPLC or mass spectrometric methods. Urinary excretion products resulting from DNA damage were also estimated (immunochemical assay, mass spectrometry). The measurement of adducts was focused on those from genotoxicants that result from petrochemical combustion or processing, e.g. low-molecular-weight alkylating agents, PAHs and compounds that cause oxidative DNA damage. Cytogenetic analysis of lymphocytes was undertaken (micronuclei, chromosome aberrations and sister chromatid exchanges) and mutation frequency was estimated at a number of loci including the hprt gene and genes involving in cancer development. Blood and urine samples from individuals exposed to urban pollution were collected. Populations exposed through occupational or medical sources to larger amounts of some of the genotoxic compounds present in the environmental samples were used as positive controls for the environmentally exposed population. Samples from rural areas were used as negative controls. The project has led to new, more sensitive and more selective approaches for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers exposed to ethylene oxide in a sterilization plant. Dose reponse and adduct repair were studied for methylated adducts in patients treated with methylating cytostatic drugs. The biomonitoring methods have also demonstrated their potential for detecting environmental exposure to genotoxic compounds in nine groups of non-smoking individuals, 32P-postlabelling of DNA adducts being shown to have the greatest sensitivity.

Antineoplastic Agents, Alkylating↗

PubMed1996

Glutathione S-transferase mu as a risk factor in bladder tumours.

Glutathione transferases are involved in the detoxification of many zenobiotica involved in the etiology of cancer. To investigate the role of the glutathione S-transferase M1 deletion (GSTM1*0/0) in bladder carcinogenesis, the polymerase chain reaction was used to determine the GSTM1 genotypes of cancer patients (n = 234) and hospital controls (n = 202). Overall, the proportion of GSTM1*0/0 in the case group was 57%, compared to 50% in the control group giving an odds ratio (OR) of 1.33, (0.91-1.94; 95% confidence interval (CI)). Dividing the bladder cancer group into incident (n = 87) and surviving case groups (n = 147), a modest association between the GSTM1*0/0 genotype and bladder cancer was found in the surviving group, whereas, in the incident group no association was found. Logistic regression analysis of the incident cases, adjusting for age, gender, and cigarette smoking, revealed ORs of 1.12 (0.61-2.08) and 0.74 (0.33-1.73) for the malignant and benign tumours, respectively. The corresponding adjusted ORs for the surviving cases were 1.81 (1.04-3.13) for benign and 1.43 (0.80-2.56) for malignant tumours. Thus, in this study, the GSTM1 deletion is not a risk factor for the development of bladder cancer, but may be related to the survival of the bladder cancer patients. This finding is very important for the design of case-control studies in general, and for the interpretation of existing data.

Aged↗

PubMed1996

Monitoring human exposure to 2-hydroxyethylating carcinogens.

It is known that human hemoglobin contains low levels of N-terminal N-(2-hydroxyethyl)valine. Possible sources of this modified amino acid are exposure to ethylene oxide or other 2-hydroxy-ethylating agents. Although such processes are likely to occur endogenously, the exogenous contribution to the adduct formation is unclear. In order to explore the latter, we have analyzed N-(2-hydroxyethyl)valine in the globin of 49 pregnant women and evaluated the effect of smoking status, area of residence, and glutathione S-transferase M1 genotype on adduct levels. Transplacental transfer of hydroxyethylating agents was also studied by the analysis of umbilical cord hemoglobin. The adduct levels in smokers were significantly higher than those in nonsmokers. The adduct levels in umbilical cord blood globin were quantitatively related to those in maternal blood (maternal:fetal ratio 2.7 in smokers and 2.8 in nonsmokers). In the nonsmokers, there was no statistically significant difference in the adduct level between the urban and rural areas, but the level in suburbia tended to be lower than that in the rural area. In the combined smoker and nonsmoker groups, there was no effect of the glutathione S-transferase M1 genotype on levels of N-(2-hydroxyethyl)valine.

Adult↗

PubMed1996

Transplacental transfer of environmental genotoxins--polycyclic aromatic hydrocarbon-albumin in nonsmoking women.

Transplacental transfer of genotoxic material has been determined by measuring the polycyclic aromatic hydrocarbon-albumin adduct level in serum isolated from the mother and the umbilical cord blood using a competitive enzyme-linked immunoadsorbent assay (ELISA) and the antibody (8E11( against benzo[a]pyrene (B[a]P) tetrols. Smoking women (median = 5.54 fmol B[a]P eq/micrograms albumin; n = 21 cases) and nonsmoking women living in rural areas (median = 4.99; n = 30) had higher adduct levels than nonsmoking women living in suburbia (median = 4.09; n = 37), whereas nonsmoking women living in the city of Aarhus had an intermediate level (median = 4.82; n = 40). The median adduct level in umbilical cord blood was significantly lower than in maternal blood, the maternal/fetal ratio being approximately 1.3. A positive association between the adduct levels in the mother and umbilical cord blood was observed. This study indicates that the competitive ELISA to detect B[a]P bound to serum albumin is sensitive enough to detect differences in the burden of genotoxic compounds in nonoccupationally exposed individuals. The lower adduct level in people living in suburbia suggests that local production of incomplete combustion products, like vehicle exhaust or heat generation, is a contributing factor to genotoxic compounds in the general environment.

Adult↗

PubMed1995

DNA and protein adducts.

Application of methods for the measurement of DNA and protein adducts in environmental studies was surveyed. The methods included the 32P-postlabelling assay, immunoassay and synchronous fluorescence spectroscopy for DNA adducts. Additionally, methods for detecting excreted urinary RNA and DNA adducts were discussed. The protein adduct techniques included both immunological and chemical assays. The techniques have been applied in occupational and environmental studies, but usually one assay at a time. As specific DNA adducts can now be assayed for, it would be important to use these methods and specific protein adduct assays in the same studies. It is important to develop further specific adduct tests. This can be done with the help of standard compounds, which also allow quantitation in the assays. An international bank of standard compounds would be a major advancement to human biomonitoring.

Biomarkers↗

PubMed1995

Effect of a negative regulatory element (NRE) on the human CYP1A1 gene expression in breast carcinoma MCF-7 and hepatoma HepG2 cells.

The expression of the cytochrome P4501A1 gene, CYP1A1, is induced by e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) mainly by transcriptional mechanisms. The inducers mediate their effect upon binding and activation of the aryl hydrocarbon receptor (AHR) transcription-factor complex. Utilizing chimeric CYP1A1/CAT constructs transient gene expression experiments indicate that the putative negative regulatory element (NRE) of CYP1A1 influence the relative TCDD induced CAT activity in HepG2 cells, whereas this effect was not observed in MCF-7 cells. Differences in the formation of cell-specific protein-DNA complexes were demonstrated by gel retardation assays suggesting a functional difference of NRE in these two cell lines.

Base Sequence↗

PubMed1995

Inhibition of intercellular communication by condensates of high and low tar cigarettes.

Inhibition of gap junctional intercellular communication (GJIC) is a predictive short term test for tumor promoting activity. A new metabolic cooperation assay has been developed, which takes the cytochrome P-450 metabolism into account. In this assay the inhibitory activity of tobacco smoke condensates (CSC) and CSC fractions from high and low tar cigarettes was tested. CSC of both high and low tar cigarettes and fractions thereof contained tumor promoting activity. The tar yield of the cigarettes did not closely reflect the effects in the GJIC assay and the major constituent nicotine had no effect. The effect was only marginally greater in cells expressing different cytochrome P-450 enzymes, indicating that the active substances are not metabolized by these enzymes. The activities of CSC fractions were considerably lower than the activities in the unfractionated CSC. This may indicate that compounds in the CSC act strongly synergistically. Furthermore, CSC and CSC fractions synergistically inhibit GJIC with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, indicating different mechanisms of action.

Cell Communication↗

PubMed1995

Repair of DNA lesions induced by ultraviolet irradiation and aromatic amines in normal and repair-deficient human lymphoblastoid cell lines.

A host cell reactivation (HCR) assay was employed to study the capacity of a normal and three repair-deficient human lymphoblastoid cell lines to repair DNA damage induced by UV irradiation and the aromatic amines 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and N-acetyl-2-aminofluorene (AAF) respectively. The cell line belonging to xeroderma pigmentosum complementation group C (XP-C) removed all three types of damage less efficiently than the normal cell line, but more efficiently than the cell line belonging to xeroderma pigmentosum complementation group D (XP-D). The cell line belonging to complementation group B of Cockayne's syndrome (CS-B) showed reduced host cell reactivation. Fibroblasts from CS-B patients have reduced gene-specific DNA repair, but normal total genomic DNA repair, thus our data suggest that the HCR assay measures the capacity for gene-specific DNA repair. In the XP-D cell line, which had practically no DNA repair capacity, AAF adducts had a more potent inhibitory effect on gene expression than UV and PhIP adducts. When corrected for this inhibitory effect, the wild-type, XP-C and CS-B cell lines repaired low levels of AAF and UV adducts with similar efficiencies, however, PhIP adducts were repaired less efficiently.

2-Acetylaminofluorene↗

PubMed1995

Transplacental transfer of environmental genotoxins: polycyclic aromatic hydrocarbon-albumin in non-smoking women, and the effect of maternal GSTM1 genotype.

Transplacental transfer of genotoxic material has been determined by measuring the polycyclic aromatic hydrocarbon-albumin adduct level in serum isolated from the mother and the umbilical cord using a competitive ELISA assay and the antibody (8E11) against benzo[a]pyrene (B[a]P) tetrols. Smoking women (median 5.54 fmol B[a]P equiv/microgram albumin; 21 cases) and non-smoking women living in rural areas (median 4.99; 30) had higher adduct levels than non-smoking women living in suburbia (median 4.09; 37), whereas non-smoking women living in the city of Aarhus had an intermediate level (median 4.82; 40). Exposure to passive smoking did not modify the adduct levels. When all non-smoking cases were combined, the transport time to/from the home became a major contributing factor to the adduct level. The median adduct level in umbilical cord blood was significantly lower than in maternal blood, the maternal/fetal ratio being approximately 1.3, and a positive association between the adduct levels in the mother and umbilical cord blood was observed. The frequency of the GSTM1 null genotype in the study population, females aged 19-44, was 55.4%, but the GSTM1 genotype did not significantly alter the serum albumin adduct level. This study indicates that the competitive ELISA to detect B[a]P bound to serum albumin is sensitive enough to detect differences in the burden of genotoxic compounds in non-occupational exposed individuals. The lower adduct level in people living in suburbia suggests that local production of incomplete combustion products, like vehicle exhaust or heat generation, is the major contributing factor to genotoxic compounds in the general environment.

Adult↗

PubMed1994

Exposure of bus and taxi drivers to urban air pollutants as measured by DNA and protein adducts.

Urinary 1-hydroxypyrene, lymphocyte DNA adducts, serum protein-bound PAH and hemoglobin-bound alkene adducts were analysed from 4 groups of non-smoking men: urban and suburban bus drivers, taxi drivers and suburban controls. The only differences between the groups were in DNA adducts between suburban bus drivers and controls, and in DNA adduct and plasma protein PAH-adducts between taxi drivers and controls.

Air Pollutants↗

PubMed1994

Exposure of iron foundry workers to polycyclic aromatic hydrocarbons: benzo(a)pyrene-albumin adducts and 1-hydroxypyrene as biomarkers for exposure.

Exposure to polycyclic aromatic hydrocarbons (PAHs) in foundry workers has been evaluated by determination of benzo(a)pyrene-serum albumin adducts and urinary 1-hydroxypyrene. Benzo(a)pyrene binding to albumin and 1-hydroxypyrene were quantitatively measured by enzyme linked immunosorbent assay (ELISA) and reverse phase high performance liquid chromatography (HPLC), respectively. 70 male foundry workers and 68 matched controls were investigated. High and low exposure groups were defined from breathing zone hygienic samples, consisting of 16 PAH compounds in particulate and gaseous phase. Mean total PAH was 10.40 micrograms/m3 in the breathing zone, and mean dust adsorbed PAH was 0.15 microgram/m. All carcinogenic PAH was adsorbed to dust. Median benzo(a)pyrene-albumin adduct concentrations (10-90% percentiles) were similar in foundry workers (smokers 0.55 (0.27-1.00) and non-smokers 0.58 (0.17-1.15)) pmol/mg albumin and age matched controls (smokers 0.57 (0.16-1.45) and non-smokers 0.70 (0.19-1.55) pmol/mg albumin). Median 1-hydroxypyrene concentrations were significantly higher (P < 0.0001) in smoking and non-smoking foundry workers (0.022 (0.006-0.075) and 0.027 (0.006-0.164)) mumol/mol creatinine than in smoking and non-smoking controls (0 (0-0.022) and 0 (0-0.010) mumol/mol creatinine). Dose-response relations between total PAH, pyrene, carcinogenic PAHs, and 1-hydroxypyrene for smokers, and polycyclic aromatic hydrocarbons adsorbed to dust for non-smokers are suggested. Exposure to PAHs adsorbed to dust showed an additive effect. There was no correlation between the concentrations of 1-hydroxypyrene and benzo(a)pyrene-albumin adducts. The change in 1-hydroxypyrene over a weekend was also studied. Friday morning median 1-hydroxypyrene concentrations were significantly higher in both smokers and non-smokers (0.021 (0-0.075) and 0.027 (0.06-0.164)) mumol/mol creatinine than Monday morning median concentrations (0.007 (0-0.021) and 0.008 (0-0.021) mumol/mol creatinine). Smoking did not affect the concentrations of 1-hydroxypyrene or benzo(a)pyrene-albumin adducts. These data suggest that 1-hydroxypyrene is a sensitive biomarker for low dose PAH exposure. Exposure to PAHs may be aetiologically related to increased risk of lung cancer in foundry workers.

Adult↗

PubMed1994

Future research needs associated with the assessment of potential human health risks from exposure to toxic ambient air pollutants.

This paper presents key conclusions and future research needs from a Workshop on the Risk Assessment of Urban Air, Emissions, Exposure, Risk Identification, and Quantification, which was held in Stockholm during June 1992 by 41 participants from 13 countries. Research is recommended in the areas of identification and quantification of toxics in source emissions and ambient air, atmospheric transport and chemistry, exposure level assessment, the development of improved in vitro bioassays, biomarker development, the development of more accurate epidemiological methodologies, and risk quantification techniques. Studies are described that will be necessary to assess and reduce the level of uncertainties associated with each step of the risk assessment process. International collaborative research efforts between industry and government organizations are recommended as the most effective way to carry out this research.

Air Pollutants↗

PubMed1993

Two phorbol ester receptor affinities in partially transformed human urothelial cells and decrease of receptor binding in desensitized cells.

The presence of specific binding sites for phorbol esters was studied in a transformed but non-tumorigenic human urothelial cell line HCV-29 by assay of specific binding of 3H-phorbol-12,13-dibutyrate (3H-PDBu) to intact living cells. 3H-PDBu bound specifically to HCV-29 cells in a saturable and competitive manner. Scatchard plot analysis of specific binding yielded a curved plot consistent with two binding sites with Kd of 11 nM and 102 nM, respectively. At saturation the corresponding PDBu binding capacities (Bmax) were 8.8 pmol/10(6) cells (5.2 x 10(6) molecules bound per cell) and 2.8 pmol/10(6) cells (1.7 x 10(6) molecules bound per cell). 3H-PDBu binding was displaced by biologically active phorbol ester tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and mezerein, but not by tumor promoters such as L-tryptophan, anthranilic acid and sodium saccharin. In cells desensitized by pretreatment with 1 microgram/ml (2 microM) TPA or PDBu for 24 h the level of binding was reduced to 28% of the level in non-exposed cells. The ability of desensitized cells to bind 3H-PDBu was gradually restored within 5-6 days. At the same time the cells became sensitive to the morphological alteration induced by PDBu. This suggests that desensitization of HCV-29 cells is due to a decreased receptor-ligand binding capacity probably associated with down regulation of the phorbol ester receptors.

Caenorhabditis elegans Proteins↗