Ah locus-associated differences in induction of sister-chromatid exchanges and in DNA adducts by benzo[a]pyrene in mice

Wielgosz, S.M.; Brauze, Damian; Pawlak, A.L.

doi:10.1016/0027-5107(91)90115-5

Cited by 7 publications

(3 citation statements)

References 33 publications

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“…For example, male DBA/2 mice given two BaP doses of either 10 or 100 mg/kg bw per day intragastrically experienced significant increases in the frequency of sister chromatid exchanges in bone marrow cells at both doses, whereas male C57BL/6J mice exhibited only a small effect at 100 mg/kg bw per day (Wielgosz et al, 1991). A single exposure of adult Brown Norway rats to BaP at 62.5 mg/kg bw intragastrically did not cause the induction of unscheduled DNA synthesis (Mullaart et al, 1989).…”

Section: Traditional Risk Assessment Approach (Ra1)mentioning

confidence: 99%

“…Intestinal cells from these adult Brown Norway rats had a significant increase in DNA single-strand breaks relative to controls at the 62.5 mg/kg bw (LOAEL) dose (Mullaart et al, 1989). Thus, the lowest LOAEL established for these genotoxicity endpoints is 10 mg/kg bw per day (Wielgosz et al, 1991), and a NOAEL was not achieved.…”

Section: Traditional Risk Assessment Approach (Ra1)mentioning

confidence: 99%

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Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Moffat

Chepelev

Labib

et al. 2015

Critical Reviews in Toxicology

140

100

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Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those applying toxicogenomics has never been done. We conducted a case study to evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene (BaP), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3) approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and mice exposed to BaP to determine if these data could provide insight into BaP's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that BaP is genotoxic in mice and allowed the development of a detailed MOA. Toxicogenomics analysis in human lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed pathways with animal tissues. Quantitatively, the PODs for traditional and transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lung 0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which applied toxicogenomics in the absence of apical toxicology data, demonstrates that this approach provides useful information in data-poor situations. Overall, our study supports the use of toxicogenomics as a relatively fast and cost-effective tool for hazard identification, preliminary evaluation of potential carcinogens, and carcinogenic potency, in addition to identifying current limitations and practical questions for future work.

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Section: Traditional Risk Assessment Approach (Ra1)mentioning

confidence: 99%

Section: Traditional Risk Assessment Approach (Ra1)mentioning

confidence: 99%

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Moffat

Chepelev

Labib

et al. 2015

Critical Reviews in Toxicology

140

100

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“…The sensitivity of this method is equivalent to the detection of 3 PAH adducts per 10 8 nucleotides. The relatively high DNA sample size (about lOO^g) required in this method is a serious limitation (16).…”

Section: Decent Advances In Dna Methodsmentioning

confidence: 99%

Molecular Epidemiology in Cancer Risk Assessment

Indulski¹,

Lutz²

1997

ACS Symposium Series

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The rapid development of molecular biology techniques has significantly aided the assessment of the detrimental consequences of chemically polluted environment on humans. It has also resulted in the development of molecular epidemiology, a new branch of epidemiology. Molecular epidemiology has become an important science which finds increasing applications in environmental monitoring. Nevertheless, a number of problems have emerged which seriously limit its practical application in epidemiologic research. Correct interpretation of test results seems to be one of the most difficult stages of assessing, by means of molecular epidemiology techniques, exposures to environmental pollutants and the resultant health effects. This refers in particular to those instances of the assessment of exposures (to environmental carcinogens for instance) for which formal exposure limits are not available. In many instances, molecular epidemiology tests are performed only because specified methods are available, but in many cases the results fail to provide any useful information. Also, the implementation of these new research methods has given rise to completely new ethical, social and legal problems. This is particularly true about research on the individual susceptibility to the adverse effects of environmental chemicals. And finally, it is extremely important to ensure that the enthusiasm about the feasibility of using the most recent molecular biology technologies does not overshadow the epidemiological problems associated with the necessity of providing suitable health care to the inhabitants of chemically polluted areas.Cancer is a long-lasting multi-stage process, and the epidemiologic data indicate that environmental chemical agents (chemical carcinogens) play an important role in this process. A chain of certain events must take place prior to carcinogenic cell transformation. The events include contact of the organism with the carcinogen, its absorption into the organism, transportation into the cells, transformation to a reactive metabolite (not all carcinogens become necessarily activated), and interaction with the critical (DNA) molecule in the target cells. The interaction results in the formation of carcinogen-DNA adducts, which in turn may lead to point mutations or breaks and/or rearrangements in the chromosomes. The changes in cellular genome DNA are not random. Usually specific genes or gene groups, which participate in the process

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Polycyclische Aromatische Kohlenwasserstoffe (PAH) [MAK Value Documentation in German language, 2008]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 45. Lieferung, Ausgabe 2008 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Wirkungsmechanismus Toxikokinetik und Metabolismus Aufnahme, Verteilung, Ausscheidung Metabolismus Erfahrungen beim Menschen Einmalige Exposition Wiederholte Exposition Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Tierexperimentelle Befunde und In‐vitro‐Untersuchungen Akute Toxizität Subakute, subchronische und chronische Toxizität Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Sonstige Wirkungen 1‐Methylpyren als Vertreter der alkylierten PAH Allgemein Metabolismus Genotoxizität Kanzerogenität Bewertung der Kanzerogenität Wirkungsbilanzen für die PAH Wirkungsäquivalente der PAH Äquivalenzfaktoren der PAH Bewertung Anhang

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Ah locus-associated differences in induction of sister-chromatid exchanges and in DNA adducts by benzo[a]pyrene in mice

Cited by 7 publications

References 33 publications

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Molecular Epidemiology in Cancer Risk Assessment

Polycyclische Aromatische Kohlenwasserstoffe (PAH) [MAK Value Documentation in German language, 2008]

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