Effect of Phenobarbital and Buthionine Sulfoximine Pretreatment on Aflatoxin B₁-Induced Glutathione S-Transferase Placental form Positive Single Hepatocytes in Rats

Abstract

Using a single dose carcinogen model developed in the rat (Moore et al., Carcinogenesis 8, 483, 1987), we have examined the effects of either phenobarbital (PB) or/and buthionine sulfoximine (BSO) pretreatment of male Fischer rats on aflatoxin B₁ (AFB₁)-induced glutathione S-transferase placental form (GST-P) positive single hepatocytes detected by the immunohistochemical method. Control rats 48 hr. after i.p. administration of AFB₁ (2 mg/kg body wt.) yielded about 10.1 ± 4.8 GST-P positive single hepatocytes/sq. cm.; PB pretreatment inhibited the generation of GST-P positive single hepatocytes to 28% of control levels. BSO pretreatment of these two groups before AFB₁ injection increased the yield of GST-P positive hepatocytes by 145% and 180% of the respective controls. There appears to be a good correlation between modulation of hepatic AFB₁-DNA binding by PB or/and BSO pretreatment and the presence of AFB₁-induced GST-P positive single hepatocytes in rats.