Glutathione S-transferase localization in aflatoxin B1-treated rat livers

TY - JOUR

T1 - Glutathione S-transferase localization in aflatoxin B1-treated rat livers

AU - Harrison, D J

AU - May, L

AU - Hayes, J D

AU - Neal, G E

PY - 1990/6

Y1 - 1990/6

N2 - 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.

AB - 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.

KW - Aflatoxin B1

KW - Aflatoxins/toxicity

KW - Animals

KW - Cells, Cultured

KW - Gene Expression

KW - Glutathione Transferase/genetics

KW - Immunohistochemistry

KW - Liver/drug effects

KW - Liver Neoplasms/chemically induced

KW - Macromolecular Substances

KW - Male

KW - Precancerous Conditions/chemically induced

KW - Rats

KW - Rats, Inbred F344

KW - Reference Values

UR - https://www.ncbi.nlm.nih.gov/pubmed/2112061

M3 - Article

C2 - 2112061

SN - 0143-3334

VL - 11

SP - 927

EP - 931

JO - Carcinogenesis

JF - Carcinogenesis

IS - 6

ER -