Biologic markers in risk assessment for environmental carcinogens

Perera, Frederica P.; Mayer, Jack; Santella, Regina M.; Brenner, D. J.; Jeffrey, Alan M.; Latriano, Louise; Smith, Steven J.; Warburton, Dorothy; Young, Tie Lan; Tsai, Wei Yann; Hemminki, Kari; Brandt‐Rauf, Paul W.

doi:10.1289/ehp.90-1519502

Cited by 18 publications

(9 citation statements)

References 30 publications

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“…In recent years, newly developed biological markers of exposure and early lesion have been increasingly applied in epidemiologic studies in order to overcome problems of statistical power in detecting minor excesses in carcinogenic risk and to better characterize and quantify the relevant exposures [see, e.g., IARC, 1988;Perera, 1988;Perera et al, 1991;Sorsa et al, 19921. In particular, DNA-PAH adducts and adducts of related agents have been successfully employed in the assessment of exposure among foundry workers in Finland [Phillips et al, 19881, coke workers in Poland [Hemminki et al, 1990a1, and humans environmentally exposed to aromatic compounds in Poland [Hemminki et al, 1990bl.…”

Section: Discussionmentioning

confidence: 99%

Cancer risk in asphalt workers and roofers: Review and meta‐analysis of epidemiologic studies

Partanen

Boffetta

1994

American J Industrial Med

190

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Twenty epidemiologic studies have described cancer risk in asphalt workers and roofers in various countries. A current concern for these workers is the potential carcinogenicity posed by inhalation of bitumen fumes or dermal exposure to bitumens. Bitumens are chemically different from many carcinogenic coal-tar based materials. Both have been employed in road paving and waterproofing. We examined and combined the results of the epidemiologic studies conducted on asphalt workers and roofers. We examined the cancer risk separately in three broad job categories: 1) roofers (exposed to bitumen fumes and previously often to coal-tar fumes); 2) highway maintenance workers (HMWs) and road pavers (exposed to bitumen fumes as well as possibly coal-tar fumes previously); and 3) miscellaneous and unspecified bitumen/asphalt workers. In roofers, an increased risk was suggested for cancers of the lung (aggregated relative risk 1.8, 95% confidence interval 1.5-2.1), stomach (1.7, 1.1-2.5), nonmelanoma skin (4.0, 0.8-12), and leukemia (1.7, 0.9-2.9). Some of the excesses may be attributable to polycyclic aromatic hydrocarbons (PAH) from coal-tar products. The aggregated relative risks in road pavers and HMWs were consistently lower than in roofers for cancers of the lung (0.9, 0.8-1.0), stomach (1.1, 0.8-1.5), bladder (1.2, 0.7-1.8), skin (2.2, 1.2-3.7), and leukemias (1.3, 0.9-1.8). Their risk of skin cancer was significantly increased, based on one study. Miscellaneous and unspecified workers had a significant excess (1.5, 1.2-1.8) of lung cancer. The data were poorly focused to address the carcinogenicity of bitumen fumes, as contrasted with tar-derived exposures. For the prospect of shedding more light on the bitumen-cancer controversy, the feasibility of a powerful multicenter cohort is currently being studied by the International Agency for Research on Cancer (IARC).

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Section: Discussionmentioning

confidence: 99%

Cancer risk in asphalt workers and roofers: Review and meta‐analysis of epidemiologic studies

Partanen

Boffetta

1994

American J Industrial Med

190

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“…Thus, adduct frequency can be employed as a useful biomarker along the continuum from exposure to pathophysiologic outcome (3,4). Moreover, it has become increasingly clear that the frequency of stable, promutagenic DNA adducts in a target tissue may also have a role in facilitating risk assessment of mutagenic carcinogens in environmental and occupational settings and, as such, DNA adduct analysis has become an essential tool in molecular epidemiology (5,6). However, since regulatory decisions are based on mutagenic activity and induced mutation frequency (MF), rather than DNA damage and adduct frequency, there is ongoing debate regarding the utility of adduct frequency metrics in a health and disease risk context.…”

Section: Introductionmentioning

confidence: 99%

Quantitative relationships betweenlacZmutant frequency and DNA adduct frequency in Muta™Mouse tissues and cultured cells exposed to 3-nitrobenzanthrone

White

Douglas

Phillips

et al. 2017

MUTAGE

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The frequency of stable DNA adducts in a target tissue can be used to assess biologically effective dose; however, the utility of the metric in a risk assessment context depends on the likelihood that the DNA damage will be manifested as mutation. Previously, we employed the Muta™Mouse system to examine the induction of lacZ mutants and DNA adducts following exposure to the well-studied mutagenic carcinogen 3-nitrobenzanthrone (3-NBA). In this follow-up work, we examined the empirical relationships between total adduct frequency and mutant frequency (MF) in tissues and cultured cells following acute 3-NBA exposure. The results show a significant induction of DNA damage and lacZ mutants in liver, colon and bone marrow, as well as FE1 pulmonary epithelial cells. In contrast, lung and small intestine samples had low, but significantly elevated adduct levels, with no significant increases in lacZ MF. Additional analyses showed a significant relationship between the mutagenic efficiency of total adducts, measured as the slope of the relationships between MF and total adduct frequency, and tissue-specific mitotic index (MI). The lack of mutation response in lung, in contrast to the high in vitro MF in FE-1 lung cells, is likely related to the 100-fold difference in MI. The lack of small intestine mutagenic response may be related to limited metabolic capacity, differences in DNA repair, and /or chemically induced apoptosis that has been observed for other potent mutagens. The results indicate that interpretation of adduct frequency values in a risk assessment context can be improved by considering the MI of the target tissue; however, more generalised interpretation is hampered by tissue-specific variations in metabolic capacity and damage processing. The work provides a proof of principle regarding the use of the Muta™Mouse system to critically examine the health risks associated with tissue-specific adduct loads.

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“…In studies on the presence of polycyclic aromatic hydrocarbon (PAH) DNA adducts in white blood cells of smokers and nonsmokers, in general, large interindividual variations were found and the identity of the adducts was not clear [Perera et al, 1991;Phillips et al, 1986Phillips et al, , 1990aStich and Dunn, 19881. Studies performed with specific white blood cell populations have also produced conflicting results.…”

Section: Introductionmentioning

confidence: 99%