Abstract
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.
Original language | English |
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Pages (from-to) | 927-31 |
Number of pages | 5 |
Journal | Carcinogenesis |
Volume | 11 |
Issue number | 6 |
Publication status | Published - Jun 1990 |
Keywords
- Aflatoxin B1
- Aflatoxins/toxicity
- Animals
- Cells, Cultured
- Gene Expression
- Glutathione Transferase/genetics
- Immunohistochemistry
- Liver/drug effects
- Liver Neoplasms/chemically induced
- Macromolecular Substances
- Male
- Precancerous Conditions/chemically induced
- Rats
- Rats, Inbred F344
- Reference Values