Future Research Needs Associated with the Assessment of Potential Human Health Risks from Exposure to Toxic Ambient Air Pollutants

Möller, Lennart; Schuetzle, Dennis; Autrup, Herman

doi:10.2307/3431952

Cited by 6 publications

(1 citation statement)

References 46 publications

(61 reference statements)

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“…The present risk estimates of environmental cancer ascribe cancers approximately equally to butadiene alone as to polycyclic aromatic matter, including PAHs (11). It is projected that butadiene is increasing overwhelmingly over polycyclic compounds; in 2010, it is estimated that butadiene alone will cause approximately five times more cancer than polycyclic material, based on a comparison of motor vehicle exhausts (11).…”

Section: Pah Adductsmentioning

confidence: 99%

Future research directions in the use of biomarkers.

Hemminki

Kumar

Bykov

et al. 1996

Environ Health Perspect

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Many DNA adduct studies have been carried out in occupational groups that have been at a risk of cancer based on epidemiological results relating to exposure decades ago. Even new epidemiological publications on cancer cannot accurately address the effective exposures after about 1970. This is one justification for biomarker studies. Another justification is exposures for which epidemiological studies have not been conducted or have provided inadequate results, in spite of suspicions raised by short-term or animal experiments. The modulation of environment carcinogenesis by host polymorphism in genes for xenobiotic metabolizing and DNA repair enzymes is currently under extensive investigation. The studies relating phenotype/genotype to cancer are presently extended to various end points that may be related to cancer such as DNA adducts and cytogenetic damage. Adjustment for a metabolic phenotype or genotype may also increase the precision in the measurement. Mutations in oncogenes and tumor suppressor genes may give clues to the etiology of cancer.

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Section: Pah Adductsmentioning

confidence: 99%

Future research directions in the use of biomarkers.

Hemminki

Kumar

Bykov

et al. 1996

Environ Health Perspect

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DNA adducts of 1,3‐butadiene in humans: Relationships to exposure, GST genotypes, single‐strand breaks, and cytogenetic end points

Zhao

Vodička

Srám

et al. 2001

Environ and Mol Mutagen

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The modulation of 1,3-butadiene (BD)-induced DNA adducts by occupational exposure, glutathione S-transferase (GST) genotypes, single-strand breaks, and cytogenetic end points was studied in 15 workers and 11 controls. The exposed group consisted of 8 smokers and 7 nonsmokers, whereas the control group consisted of 7 nonsmokers and 4 smokers. Among all subjects, the adduct levels in workers lacking GSTM1 were significantly higher than in those who were GSTM1 positive (P = 0.026), and individuals with combined GSTM1(-) and GSTT1(+) genotype had elevated level of adducts compared to that of persons with GSTM1(+) and GSTT1(+) (P = 0.049). The increase in BD-DNA adduct levels in all subjects was significantly related to BD exposure and GSTM1 genotype (linear multiple regression analysis, P = 0.001; P = 0.035). The results suggest that DNA adducts serve as a sensitive and specific biomarker, integrating exposure and host metabolic capacity, although the data are limited to a small number of subjects.

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Markers of individual susceptibility and DNA repair rate in workers exposed to xenobiotics in a tire plant

Vodička

Kumar

Štětina

et al. 2004

Environ and Mol Mutagen

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Workers employed in tire plants are exposed to a variety of xenobiotics, such as 1,3-butadiene (BD), soots containing polycyclic aromatic hydrocarbons, and other organic chemicals (e.g., styrene). In the present study, we investigated markers of genotoxicity [chromosomal aberrations (CAs) and single-strand breaks (SSBs)] in a cohort of 110 tire plant workers engaged in jobs with different levels of xenobiotic exposure in relation to various polymorphisms in genes coding for biotransformation enzymes (CYP1A1, CYP2E1, EPHX1, GSTM1, GSTP1, and GSTT1) and in genes involved in DNA repair (XPD exon 23, XPG exon 15, XPC exon 15, XRCC1 exon 10, and XRCC3 exon 7). In addition, the expression of CYP2E1, a gene playing a key role in BD metabolism, was determined by real-time PCR in peripheral blood lymphocytes, and the capacity of lymphocytes to repair gamma-ray-induced SSBs and to convert 8-oxoguanine in HeLa cell DNA into SSBs was assessed using in vitro assays. No positive associations were detected between the CA frequency or SSB induction and levels of workplace exposure; however, a nonsignificant twofold higher irradiation-specific DNA repair rate was found among highly exposed workers. In evaluations conducted with the markers of individual susceptibility, workers with low-EPHX1-activity genotypes exhibited a significantly higher CA frequency as compared to those with medium and high-EPHX1-activity genotypes (P = 0.050). CA frequencies were significantly lower in individuals homozygous for the XPD exon 23 variant allele in comparison to those with the wild-type CC genotype (P = 0.003). Interestingly, CAs were higher in individuals with higher CYP2E1 expression levels, but the association was nonsignificant (P = 0.097). The results from this study suggest the importance of evaluating markers of individual susceptibility, since they may modulate genotoxic effects induced by occupational exposure to xenobiotics.

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Future Research Needs Associated with the Assessment of Potential Human Health Risks from Exposure to Toxic Ambient Air Pollutants

Cited by 6 publications

References 46 publications

Future research directions in the use of biomarkers.

Future research directions in the use of biomarkers.

DNA adducts of 1,3‐butadiene in humans: Relationships to exposure, GST genotypes, single‐strand breaks, and cytogenetic end points

Markers of individual susceptibility and DNA repair rate in workers exposed to xenobiotics in a tire plant

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