Structural basis for the induction of preneoplastic glutathione S-transferase positive foci by hepatocarcinogens.
A data base consisting of 100 chemicals tested for the ability to enhance the formation of glutathione-S-transferase (GST) positive preneoplastic lesions were analyzed by the CASE structure-activity relational system. A number of structural determinants associated with the induction of GST-positive foci were recognized. The majority of these describe non-electrophilic moieties. It is concluded that there is a structural basis for the induction of these neoplastic lesions; interestingly, it was found that this activity is associated with structures that are non-electrophilic. Reconstruction experiments have indicated that the identified structures are meaningful and that their significance could be better understood with the availability of test results on additional chemicals.
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15238.
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Sakai
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Klopman
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Rosenkranz
D002273:Carcinogens / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism*; D008099:Liver / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D011230:Precancerous Conditions / Q000139:chemically induced*; D012984:Software; D013329:Structure-Activity Relationship
D002273:Carcinogens; D005982:Glutathione Transferase