Pretreatment with mixed‐function oxidase inducers increases the sensitivity of the hepatocyte/DNA repair assay

Shaddock, Joseph G.; Heflich, Robert H.; McMillan, David C.; Hinson, Jack; Casciano, Daniel A.

doi:10.1002/em.2850130402

Cited by 25 publications

(8 citation statements)

References 39 publications

(15 reference statements)

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“…Briefly, in the in vitro hepatocyte DNA repair assay, freshly isolated cells were incubated for 18 h in Williams medium E with the test chemical and 10/aCi]ml3H-thymidine. In some cases the animals were given dioxane in the drinking water prior to hepatocyte isolation to provide the opportunity for enzyme induction or other physiological changes that might yield increased genotoxicity (Shaddock 1988). Rats consumed approximately 25 ml/day of water containing 1% dioxane compared to controls of approximately 39 ml/day.…”

Section: Methodsmentioning

confidence: 99%

“…978). These conditions were examined because of the possibility of production of genotoxic metabolites in the induced state (Shaddock et al 1988). The proposed metabolite dioxane-2-one produced no DNA repair in primary hepatocyte cultures at doses up to 1.0 mM in naive rats or at doses up to 0.5 mM in cells isolated from animals pretreated with 2% dioxane in the drinking water for 1 week (Table 1).…”

Section: Hepatocyte Dna Repairmentioning

confidence: 99%

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Examination of potential mechanisms of carcinogenicity of 1,4-dioxane in rat nasal epithelial cells and hepatocytes

et al. 1991

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Several long-term studies with 1,4-dioxane (dioxane) have shown it to induce liver tumors in mice, and nasal and liver tumors in rats when administered in amounts from 0.5 to 1.8% in the drinking water (Argus et al. 1965; Kociba et al. 1974; National Cancer Institute, 1978). In order to examine potential mechanisms of action, chemically-induced DNA repair (as an indicator of DNA reactivity) and cell proliferation (as an indicator of promotional activity) were examined in nasal turbinate epithelial cells and hepatocytes of male Fischer-344 rats treated with dioxane. Neither dioxane nor 1,4-dioxane-2-one, one of the proposed metabolites, exhibited activity in the in vitro primary rat hepatocyte DNA repair assay, even from cells that had been isolated from animals given either 1 or 2% dioxane in the drinking water for 1 week to induce enzymes that might be responsible for producing genotoxic metabolites. No activity was seen in the in vivo hepatocyte DNA repair assay in animals given a single dose of up to 1000 mg/kg dioxane or up to 2% dioxane in the drinking water for 1 week. Treatment of rats with 1.0% dioxane in the drinking water for 5 days yielded no increase in liver/body weight nor induction of palmitoyl CoA oxidase, indicating that dioxane does not fit into the class of peroxisomal proliferating carcinogens. The percentage of cells in DNA synthesis phase (S-phase) was determined by administration of 3H-thymidine and subsequent quantitative histoautoradiography. The hepatic labeling index (LI) did not increase at either 24 or 48 h following a single dose of 1000 mg/kg dioxane.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Methodsmentioning

confidence: 99%

Section: Hepatocyte Dna Repairmentioning

confidence: 99%

Examination of potential mechanisms of carcinogenicity of 1,4-dioxane in rat nasal epithelial cells and hepatocytes

et al. 1991

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“…However, when hepatocytes from rats pretreated with Aroclor-1254 were used, exposure of the cells to 4,4'-oxydianiline in vitro resulted in a concentration-dependent increase in UDS. Likewise, in hepatocytes from rats pretreated with phenobarbital, 4,4'-oxydi-aniline induced a dose-dependent increase in DNA repair [19]. The UDS test yielded weak positive results with 4,4'-oxydianiline when it was carried out with hepatocytes from ACI/N rats [20].…”

Section: Genotoxicitymentioning

confidence: 98%

4,4′‐Oxydianiline [MAK Value Documentation, 1993]

2012

The MAK‐Collection for Occupational Health and Safety

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Published in the series Occupational Toxicants , Vol. 6 (1993) The article contains sections titled: Toxic Effects and Modes of Action Pharmacokinetics Effects in Man Effects on Animals Acute toxicity Dermal toxicity Subchronic and chronic toxicity Sensitization tests Genotoxicity Carcinogenicity Manifesto (MAK value, classification)

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“…HID, highest effective dose; LED, lowest effective dose; MED, maximum effective dose; PCDD/PCDF, polychlorinated dibenzodioxin/polychlorinated dibenzofuran; TEQ, toxic equivalency Unscheduled DNA synthesis, Sprague-Dawley rat, primary hepatocytes -300 ip × 1 Kornbrust & Dietz (1985) Unscheduled DNA synthesis, rat, primary hepatocytes -500 ip × 1 Shaddock et al (1989) Unscheduled DNA synthesis, male cynomolgus monkey, primary hepatocytes For the nomenclature of PCB metabolites, the reader is referred to the review by Grimm et al (2015). Table 1.1, Section 1.…”

Section: Non-mammalian Systemsmentioning

confidence: 99%

“…When used for hepatic enzyme induction, a single intraperitoneal application of Aroclor 1254 of up to 500 mg/kg bw in rats (Kornbrust & Dietz, 1985;Shaddock et al, 1989) Gauger et al (2004), Miyazaki et al (2004) DAT or VMAT Dopamine active transporter or vesicular monoamine transporters Coplanar and multi-ortho-PCBs Decrease or increase in dopamine levels Bemis & Seegal (2004), Richardson & Miller (2004), Seegal et al (2005) GR Glucocorticoid receptor MeSO 2 -PCBs, OH-PCBs, PCB-28, PCB-153, PCB-118…”

mentioning

confidence: 99%

Polychlorinated biphenyls and polybrominated biphenyls

Walker¹

2001

Organic Pollutants

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initiated a programme on the evaluation of the carcinogenic risk of chemicals to humans involving the production of critically evaluated monographs on individual chemicals. The programme was subsequently expanded to include evaluations of carcinogenic risks associated with exposures to complex mixtures, lifestyle factors and biological and physical agents, as well as those in specific occupations. The objective of the programme is to elaborate and publish in the form of monographs critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations; to evaluate these data in terms of human risk with the help of international working groups of experts in carcinogenesis and related fields; and to indicate where additional research efforts are needed. The lists of IARC evaluations are regularly updated and are available on the Internet at http:// monographs.iarc.fr/.This programme has been supported since 1982 by Cooperative Agreement U01 CA33193 with the United States National Cancer Institute, Department of Health and Human Services. Additional support has been provided since 1986 by the European Commission Directorate-General for Employment, Social Affairs, and Inclusion, initially by the Unit of Health, Safety and Hygiene at Work, and since 2014 by the European Union Programme for Employment and Social Innovation "EaSI" (2014-2020) The International Agency for Research on Cancer welcomes requests for permission to reproduce or translate its publications, in part or in full. Requests for permission to reproduce or translate IARC publications -whether for sale or for non-commercial distribution -should be addressed to the IARC Communications Group at: publications@iarc.fr.The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.The IARC Monographs Working Group alone is responsible for the views expressed in this publication. IARC Library Cataloguing in Publication Data NOTE TO THE READERThe term 'carcinogenic risk' in the IARC Monographs series is taken to mean that an agent is capable of causing cancer. The Monographs evaluate cancer hazards, despite the historical presence of the word 'risks' in the title.Inclusion of an agent in the Monographs does not imply that it is a carcinogen, only that the published data have been examined. Equally, the fact that an agent has not yet been evaluated in a Monograph does not mean that...

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Pretreatment with mixed‐function oxidase inducers increases the sensitivity of the hepatocyte/DNA repair assay

Cited by 25 publications

References 39 publications

Examination of potential mechanisms of carcinogenicity of 1,4-dioxane in rat nasal epithelial cells and hepatocytes

Examination of potential mechanisms of carcinogenicity of 1,4-dioxane in rat nasal epithelial cells and hepatocytes

4,4′‐Oxydianiline [MAK Value Documentation, 1993]

Polychlorinated biphenyls and polybrominated biphenyls

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