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.
Sakai
T
T
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15238.
Klopman
G
G
Rosenkranz
H S
HS
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