Quantitation of polycyclic aromatic hydrocarbons, 1-hydroxypyrene, and mutagenicity in urine of coal tar-treated psoriasis patients and untreated volunteers. (65/76)

Coal tar-treated psoriasis patients were used as a model population to test a newly developed enzyme-linked immunosorbent assay (ELISA) for urinary excretion of benzo(a)pyrene and related polycyclic aromatic hydrocarbons (PAHs). The ability of the ELISA to detect exposure was also compared with that of two previously established biomonitoring methods, measurement of urinary 1-hydroxypyrene by high performance liquid chromatography with fluorescence detection and mutagenicity measured by the Salmonella typhimurium mutagenesis assay. Urine samples were collected from 57 patients and 53 untreated volunteers. Urinary excretion of PAH metabolites, measured by competitive ELISA with a monoclonal antibody (4D5), was elevated in patients (mean, 730 +/- 1370 mumol/mol creatinine) compared with untreated volunteers (110 +/- 90 mumol/mol creatinine; P < 0.0001). 1-Hydroxypyrene also was elevated in patients (mean, 547 +/- 928 mumol/mol creatinine) compared with volunteers (mean, 0.14 +/- 0.17 mumol/mol creatinine; P < 0.0001). Much larger differences between mean values in patients and volunteers were observed with the 1-hydroxypyrene assay compared with the PAH metabolite ELISA. No significant effect of smoking could be detected by either assay. Analysis by the Salmonella typhimurium mutagenesis assay indicated elevated mutagenicity in urine from patients (1410 +/- 2750 revertants/mmol creatinine) compared with volunteers (715 +/- 846 revertants/mmol creatinine; P = 0.072). In all subjects, there was a good correlation between the PAH metabolites and both 1-hydroxypyrene (r = 0.717; P < 0.0001) and urinary mutagenicity (r = 0.317; P = 0.004). These results suggest that the ELISA, which easily can be carried out on large numbers of samples, can be used for monitoring urinary excretion of PAHs in a high exposure population. Ongoing studies are designed to determine its applicability to lower exposure populations.  (+info)

Tumorigenicity of a combination of psoriasis therapies. (66/76)

Coal tar, a tumour initiator, and dithranol, a tumour promoter, are used in the treatment of psoriasis. Topical treatment of mice with pharmaceutical formulations of these two agents, at therapeutic doses, induced skin papillomas in a classical two-stage carcinogenesis protocol, while treatment with either agent alone did not. This finding has implications for the use of both agents in combination in the treatment of psoriasis.  (+info)

Natural selection of PAH-degrading bacterial guilds at coal-tar disposal sites. (67/76)

Microbial activity patterns at buried coal-tar disposal sites have been under investigation for several years to determine the response of naturally occurring microflora to polycyclic aromatic hydrocarbons (PAHs) at the sites. At one site in upstate New York, data have shown enrichment of PAH-degrading bacteria in subsurface contaminated zones but not in uncontaminated zones. Similar work at a midwestern site showed that the same trends existed in a heterogeneous disposal site except that a borehole outside the plume showed some PAH-mineralization activity. Polymerase chain reaction amplification of DNA extracted from sediment samples from the New York site indicated the presence of naphthalene metabolism genes nahAc and nahR, similar to those found on the NAH7 plasmid of Pseudomonas putida G7. Significant sequence polymorphism was observed in amplified nahAc products, indicating that divergent homologs of nahAc were present in the native community. Protozoan numbers were elevated in sediment samples displaying relatively high PAH-degrading activity, suggesting that a food chain was established based on PAH-degrading bacteria. Removal of the coal-tar source at the site occurred in 1991. In 1992, sampling of three key borehole stations revealed that mixing and backfilling operations had introduced soil microorganisms into the source area and introduced 14C-PAH-mineralization activity into the previously inactive pristine area. Thus removal of the source of the contaminants and restoration at the site have altered the microbial activity patterns outside the contaminant plume as well as in the source area.  (+info)

Compensating lung cancer patients occupationally exposed to coal tar pitch volatiles. (68/76)

OBJECTIVES: To investigate the process of deciding on compensation claims by lung cancer patients exposed occupationally to coal tar pitch volatiles. METHODS: For each case of lung cancer the probability that it was caused (probability of causation (PC)) by coal tar pitch volatiles was expressed as an increasing function of cumulative exposure to benzo-a-pyrene-years. This was assessed from several exposure-response models fitted to data from a large epidemiological study of aluminum production workers. For some models, PC depended also on the smoking habit of the cancer patient. RESULTS: Estimation of relative risk by exposure group indicated that over 50% of lung cancers were attributable to coal tar pitch volatiles (PC > 50%) at exposures above 100 micrograms/m3-years benzo(a)pyrene. A linear relative risk model indicated that 50% PC was first achieved at 342.2 micrograms/m3-years benzo(a)pyrene, or 190.1 micrograms/m3-years benzo(a)pyrene according to the upper 95% confidence limit for risk increment. Corresponding figures for a power curve model were 210.3 and 45.9. With these five figures as compensation criteria compensation would have resulted in 31.4%, 2.7%, 19.2%, 15.7%, and 39.2% of cancers studied, compared with an estimated total proportion of cancers studied attributable to coal tar pitch volatiles of 15%-26%. If risks due to coal tar pitch volatiles and smoking multiply, PC does not depend on the amount smoked. If the two risks are additive, however, PC depends on the amount smoked according to a formula, with the figures mentioned applying to an average smoking history (24.4 pack-years). CONCLUSION: Because of its simplicity and because it falls within the range of criteria based on several more sophisticated approaches, we prefer the criterion of 100 micrograms/m3-years, based on the relative risks by exposure group. However, the compensation board of the Canadian province of Quebec, on consideration of these alternatives, has proposed as a criterion that the upper 95% confidence limit of PC for the patient be at least 50%, assuming an additive relative risk model and allowing for their smoking habit.  (+info)

Carcinogenicity of benzo[a]pyrene and manufactured gas plant residues in infant mice. (69/76)

The present study determined tumorigenicity, tumor classification and DNA damage induced in infant mice by benzo[a]pyrene (B[a]P) or Manufactured Gas Plant (MGP) residues after a single exposure. Male and female B6C3F1 mice were exposed to B[a]P or MGP residue from a single environmental site (MGP-4) and males were also exposed to MGP residue composite from seven different sites (MGP-M7). At 26, 39 and 52 weeks after exposure tumorigenesis was assessed in lung, forestomach and liver. Formation and persistence of DNA adducts were quantified by 32P-postlabeling. Exposure of males to B[a]P induced liver tumors in a dose and time dependent manner. MGP induced more advanced tumors than B[a]P. Only a single liver tumor was found in MGP-4 treated females. No forestomach and few pulmonary adenomas were induced in males or females. MGP-4, MGP-M7 or B[a]P induced DNA adducts in males and females. Adducts in liver, lung and forestomach peaked on different days and decreased at different rates. At 24 h post-exposure, no significant differences in initial DNA adduct levels occurred in males and females exposed to MGP-4 or B[a]P. Lack of DNA damage (adducted DNA) did not account for non-responsiveness of lung and forestomach in B6C3F1 genders as well as in liver in females. MGP tumorigenicity could not be accounted for solely by B[a]P content nor did it reflect additivity of B[a]P and other carcinogenic polycyclic aromatic hydrocarbons (PAHs) in MGP. Synergy among MGP-PAHs, presence of unidentified carcinogens and/or promoters in MGP may account for MGP potency. The B6C3F1 infant male model is a convenient and rapid assay for assessing MGP liver tumorigenicity and potency.  (+info)

Natural horizontal transfer of a naphthalene dioxygenase gene between bacteria native to a coal tar-contaminated field site. (70/76)

Horizontal transfer of genes responsible for pollutant biodegradation may play a key role in the evolution of bacterial populations and the adaptation of microbial communities to environmental contaminants. However, field evidence for horizontal gene transfer between microorganisms has traditionally been very difficult to obtain. In this study, the sequences of the 16S rRNA and naphthalene dioxygenase iron-sulfur protein (nahAc) genes of nine naphthalene-degrading bacteria isolated from a coal tar waste-contaminated site, as well as a naphthalene-degrading bacterium from a contaminated site in Washington state and two archetypal naphthalene-degrading strains, were compared. Seven strains from the study site had a single nahAc allele, whereas the 16S rRNA gene sequences of the strains differed by as much as 7.9%. No nahAc alleles from the site were identical to those of the archetypal strains, although the predominant allele was closely related to that of Pseudomonas putida NCIB 9816-4, isolated in the British Isles. However, one site-derived nahAc allele was identical to that of the Washington state strain. Lack of phylogenetic congruence of the nahAc and 16S rRNA genes indicates that relatively recent in situ horizontal transfer of the nahAc gene has occurred, possibly as a direct or indirect consequence of pollutant contamination. Alkaline lysis plasmid preparations and pulsed-field gel electrophoresis have revealed the presence of plasmids ranging in size from 70 to 88 kb in all site isolates. Southern hybridizations with a 407-bp nahAc probe have suggested that the nahAc gene is plasmid borne in all the site isolates but one, a strain isolated from subsurface sediment 400 m upstream from the source of the other site isolates. In this strain and in the naphthalene-degrading strain from Washington state, nahAc appears to be chromosomally located. In addition, one site isolate may carry nahAc on both chromosome and plasmid. Within the group of bacteria with identical nahAc sequences the Southern hybridizations showed that the gene was distributed between plasmids of different sizes and a chromosome. This suggests that plasmid modification after transfer may have been effected by transposons. Horizontal transfer of catabolic genes may play a significant role in the acclimation of microbial communities to pollutants.  (+info)

A comparison of the tumors induced by coal tar and benzo[a]pyrene in a 2-year bioassay. (71/76)

The tumorigenicity of two coal tar mixtures was compared to that of benzo[a]pyrene after 2 years of feeding. Mixture 1, a composite of coal tar from seven coal gasification plant waste sites, was fed to female B6C3F1 mice (48 mice per group) for 2 years at doses of 0.0, 0.01, 0.03, 0.1, 0.3, 0.6 and 1.0%. Mixture 2, which was composed of coal tar from two of the seven waste sites and another site having a high benzo[a]pyrene content, was fed at doses of 0.0, 0.03, 0.1 and 0.3%. Additional groups of mice were fed 0, 5, 25 and 100 ppm benzo[a]pyrene. The coal tar diets induced a dose-related increase in hepatocellular adenomas and carcinomas, alveolar/bronchiolar adenomas and carcinomas, forestomach squamous epithelial papillomas and carcinomas, small intestine adenocarcinomas, histiocytic sarcomas, hemangiosarcomas in multiple organs and sarcomas. Benzo[a]pyrene treatment resulted in an increased incidence of papillomas and/or carcinomas of the forestomach, esophagus and tongue. A comparison of the results indicated that the benzo[a]pyrene in the coal tar diets could be responsible for the forestomach tumors. In contrast, the lung and liver tumors appeared to be due to other genotoxic components contained within the coal tar mixture, while the small intestine tumors resulted from chemically-induced cell proliferation that occurred at high doses of coal tar.  (+info)

Urinary naphthols as an indicator of exposure to naphthalene. (72/76)

OBJECTIVE: The relationship between exposure to naphthalene and urinary excretion of naphthols was examined. METHODS: Concentrations of naphthalene and naphthols in breathing-zone air during a workshift and 1-naphthol and 2-naphthol in urine collected after the workshift were determined for 102 male workers. Gas chromatography with a flame ionization detector (GC-FID) was used to determine the air concentration. Urine naphthols were extracted after acid hydrolysis by solid-phase extraction and separated by the GC-FID method. Naphthalene homologues in air and their metabolites in urine samples were identified by gas chromatography-mass spectrometry. RESULTS: 1-Naphthol, 2-naphthol and 1,4-naphthoquinone were identified in the urine samples. The time-weighted average concentrations of naphthalene and naphthols in the breathing-zone air showed that the exposure level of the workers was rather low. The geometric mean values were as follows: 0.77 and 0.87 mg/m3 for naphthalene, 0.016 and 0.034 mg/m3 for 1-naphthol, 0.012 and 0.067 mg/m3 for 2-naphthol during tar distillation and naphthalene oil distillation, respectively. The corresponding urinary concentrations of 1- and 2-naphthols were 693.1 and 264.4 micromol/mol and 264.4 and 297.7 micromol/mol creatinine, respectively. The correlation coefficients between the naphthol concentrations in urine and the breathing-zone air concentrations of naphthalene were statistically significant, varying in the range of 0.64--0.75 for 1-naphthol and 0.70--0.82 for 2-naphthol. There was linear dependence (r = 0.76) between the summary concentration of naphthols in urine and the naphthalene concentration in air. CONCLUSIONS: Workers in tar distillation and naphthalene distillation are exposed to rather low concentrations of naphthalene and methylated naphthalenes and naphthols. Naphthols and 1,4-naphthoquinone identified in the urine appear to be the products of the hydroxylation of naphthalene present in the breathing-zone air. These findings suggest that the summary concentration of naphthols in urine can be used as a biomarker for naphthalene exposure.  (+info)