Glutathione S-transferase localization in aflatoxin B1-treated rat livers.
Overexpression of detoxication enzymes is associated with the development of drug-resistant, preneoplastic nodules in the carcinogen-treated rat liver. The most consistent marker of preneoplasia in many experimental models is increased expression of the pi-class glutathione S-transferase (GST) YfYf. We have confirmed by immunostaining that the pi-class GST is overexpressed in aflatoxin B1-induced preneoplastic nodules and liver tumours in rats. However, pi-class GST YfYf has low activity against aflatoxin B1-8,9-epoxide, and most activity against this cytotoxic and genotoxic metabolite is associated with the alpha-class GSTs YaYa, YaYc and YcYc. We have demonstrated that there is also a consistent increase in the alpha-class GSTs in this model. It seems likely that the overexpression of the Ya and Yc subunits, rather than increased levels of the pi-class GST YfYf, is responsible for the acquisition of a drug-resistant phenotype in rat liver preneoplastic nodules and tumours induced by aflatoxin B1.
Harrison
D J
DJ
University Department of Pathology, University of Edinburgh, UK.
May
L
L
Hayes
J D
JD
Neal
G E
GE
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D005982:Glutathione Transferase / Q000235:genetics*; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D046911:Macromolecular Substances; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values
D000348:Aflatoxins; D046911:Macromolecular Substances; D016604:Aflatoxin B1; D005982:Glutathione Transferase