Chemical and Biochemical Dosimetry of Exposure to Genotoxic Chemicals

Wogan, Gerald N.; Gorelick, Nancy J.

doi:10.2307/3430088

Cited by 28 publications

(23 citation statements)

References 27 publications

(30 reference statements)

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“…Although (±)-anti-BaPDE binds with proteins and RNA, its interaction with nucleophilic sites in DNA to form adducts has been established as a critical event as far as the initiation of carcinogenesis is concerned (Singh et al, 1998). It is well established that the degree of carcinogenicity is directly proportional to the extent of DNA adduct formation (Wogan and Gorelick, 1985). Therefore, in the present investigation, the extent of DNA adduct formation has been taken as an index for the initiation of carcinogenesis.…”

Section: Discussionmentioning

confidence: 96%

“…These adducts may lead to gene mutations and certain mutations have been known to play a critical role in the initiation phase of carcinogenesis (Dipple, 1991). It has also been reported that the degree of carcinogenicity is directly proportional to the extent of DNA adduct formation (Wogan and Gorelick, 1985). So, it seems to be quite reasonable to consider the extent of DNA adduct formation as an index for initiation of the process of carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Preventive effects of Azadirachta indica on benzo(a)pyrene‐DNA adduct formation in murine forestomach and hepatic tissues

Gangar

Sandhir

Vijay

et al. 2006

Phytotherapy Research

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In the present investigation, the effects of aqueous Azadirachta indica leaf extract (AAILE) on (3)H-benzo(a)pyrene-DNA [(3)H-B(a)P-DNA] adduct formation, the status of biotransformation enzymes and reduced glutathione (GSH) content were evaluated in the forestomach and liver of Balb/c mice. Two weeks of AAILE treatment reduced the (3)H-B(a)P-DNA adduct levels by 31.6% in forestomach tissue. Similarly, (3)H-B(a)P-DNA adduct levels were decreased by 34.7% in the liver of AAILE treated mice compared with their control counterparts. After AAILE treatment, the cytochrome P450 content decreased, whereas the GSH content increased significantly in the hepatic tissue. In the forestomach as well as in the liver, the cytochrome b5 content declined, whereas an increase in glutathione-S-transferase (GST) activity was observed in both tissues. These observations suggested that AAILE may have reduced the metabolic activation of (3)H-B(a)P with enhanced detoxification of its active metabolites, hence the observed decrease in the levels of (3)H-B(a)P-DNA adducts. These molecular and biochemical modulations observed at the initiation phase of carcinogenesis seems to be significant and could be correlated with the chemopreventive effects of A. indica against B(a)P induced forestomach tumorigenesis.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Preventive effects of Azadirachta indica on benzo(a)pyrene‐DNA adduct formation in murine forestomach and hepatic tissues

Gangar

Sandhir

Vijay

et al. 2006

Phytotherapy Research

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“…SRM 1649). These studies have shown that very little directacting mutagenicity is present in the basic fractions (94).…”

Section: Identification Of Genotoxic Agents In Ambient Airmentioning

confidence: 99%

“…The bioassay-directed chemical analysis technique has been most successful for the identification of genotoxic compounds in source samples (56, 85,90,94). Much of this work has been done on diesel exhaust.…”

Section: Identification Of Genotoxic Agents In Ambient Airmentioning

confidence: 99%

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Genetic Toxicology of Complex Mixtures

Waters¹,

Daniel²,

Lewtas³

et al. 1990

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A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. All rights reservedNo part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher FOREWORD Contained in this volume are the proceedings of the international conference on the "Genetic Toxicology of Complex Mixtures," held from July 4-7, 1989, in Washington, DC. This meeting was a satellite of the "Fifth International Conference on Environmental Mutagens" and the seventh in a biennial series of conferences on "Short-term Bioassays in the Analysis of Complex Environmental Mixtures."Our central objective in calling together key researchers from around the world was to extend our knowledge of the application of the methods of genetic toxicology and analytical chemistry in the evaluation of chemical mixtures as they exist in the environment. This conference emphasized the study of genotoxicants in air and water, and the assessment of human exposure and cancer risk. The latest strategies and methodologies for biomonitoring of genotoxicants (including transformation products) were described in the context of the ambient environment. Source characterization and source apportionment were discussed as an aid to understanding the origin and relative contribution of various kinds of complex mixtures to the ambient environment. Similarly, investigations of genotoxicants found in the indoor environment (sidestream cigarette smoke) and in drinking water (chlorohydroxyfuranones) were given special attention in terms of their potential health impacts. New molecular techniques were described to enable more precise quantitation of internal dose and doseto-target tissues.The emphasis of presentations on exposures/effects assessment was on integrated quantitative evaluation of human exposure and potential health effects. It is clear that the sophistication of complex mixture research technologies has increased dramatically since the first conference in 1978 with the application of state-of-the-art genetic and molecular methods. It is now apparent that interdisciplinary approaches are essential in order to assess the contribution of mixtures of genotoxic agents in the environment to total human exposure and potential cancer risk.We are indebted to the speakers and chairpersons who presented their data at the meeting and in the excellent chapters that follow.

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5‐Methyl deoxycytidine content of DNA from bluegill sunfish (Lepomis macrochirus) exposed to benzo[a]pyrene

Shugart

1990

Enviro Toxic and Chemistry

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The 5‐methyl deoxycytidine (m5‐dCyd) content of DNA from bluegill sunfish chronically exposed to benzo[a]pyrene at a concentration of 1 μg/L in their water for a period of 40 d was quantified by cation exchange chromatography. Hypomethylation, as measured by the loss of m5‐dCyd from the DNA, occurred shortly after benzo[a]pyrene (BaP) exposure and continued even upon termination of exposure conditions. The onset and persistence of hypomethylation was found to be correlated with other types of DNA‐damaging events such as strand breaks and DNA adduct formation. These observations suggest that changes in DNA integrity, including hypomethylation, are indicative of a biological response to genotoxic agents.

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Chemical and Biochemical Dosimetry of Exposure to Genotoxic Chemicals

Cited by 28 publications

References 27 publications

Preventive effects of Azadirachta indica on benzo(a)pyrene‐DNA adduct formation in murine forestomach and hepatic tissues

Preventive effects of Azadirachta indica on benzo(a)pyrene‐DNA adduct formation in murine forestomach and hepatic tissues

Genetic Toxicology of Complex Mixtures

5‐Methyl deoxycytidine content of DNA from bluegill sunfish (Lepomis macrochirus) exposed to benzo[a]pyrene

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