1. UDP-glucuronyltransferase activity was studied in hepatic microsomal preparations isolated from female Sprague-Dawley rats treated with either 3-methylcholanthrene, butylated hydroxyanisole, propyl gallate, ethoxyquin or a combination of 3-methylcholanthrene and butylated hydroxyanisole. 2. The substrates p-nitrophenol, 1-naphthol and phenolphthalein were used. With p-nitrophenol all treatments, except propyl gallate, caused a significant increase in activity over the control value; the combined treatment of 3-methylcholanthrene and butylated hydroxyanisole gave an additive response when compared to each treatment used singly. With 1-naphthol as substrate, 3-methylcholanthrene and 3-methylcholanthrene + butylated hydroxyanisole caused 8-fold increases in activity compared to the 2-3 fold increased caused by the other treatments. When phenolphthalein was used, all treatments increased activity to the same extent. 3. When the assays were repeated with various concentrations of each substrate, the results revealed that, except where phenolphthalein was used, distinguishable differences in the activity of each microsomal preparation were discernible, the most significant being the bimodal response of each preparation to low and high concentrations of p-nitrophenol.

Neonatal exposure of rats to xenobiotics has been shown to produce long-term alterations in hepatic enzyme activities and in levels of DNA adducts following carcinogen exposure. We exposed newborn male rats to diethylstilbestrol (DES), pregnenolone-16 alpha-carbonitrile, 7,12-dimethylbenz[a]anthracene or phenobarbital on days 1, 3 and 5 of age. At five months of age, males were injected with 1 mg/kg of [3H]aflatoxin B1 (AFB1), killed after 2 h and examined for AF-DNA adduction in the liver. Males neonatally exposed to DES showed a 35% decrease in DNA adduction levels. Analysis of the adducted DNA bases failed to show any changes in relative proportions of individual adducts in the DES samples compared to controls. Hepatic glutathione concentrations were unchanged. However, Western blot analysis of alpha-class glutathione S-transferases (alpha GST), enzymes known to inactivate the toxic AFB1-8,9-epoxide, showed a 2-fold increase in subunit levels in the DES-treated males, suggesting that the detoxifying activity of the cytosol may have been increased. To confirm this, in vitro tests were undertaken using butylated hydroxyanisole (BHA) induced mouse microsomes to activate [3H]AFB1 in the presence of treated cytosol and GSH. Analysis of metabolites by HPLC showed that DES-treated males formed 245% of the AFB-SG conjugate relative to vehicle controls. These results indicate that neonatal DES treatment resulted in long-term changes in basal alpha GST levels and suggest that these changes were responsible for lower levels of DNA adduction following adult exposure to AFB1.