Aryl hydrocarbon (benzo[a]pyrene) hydroxylase in rat mammary tissue during pregnancy and lactation

Abstract

Rats are highly resistant to mammary tumour induction by polycyclic aromatic hydrocarbons during pregnancy and lactation. Since local changes in hydrocarbon metabolism in mammary tissue or altered hepatic metabolism might contribute to the resistance, aryl hydrocarbon hydroxylase (AHH) activity in microsomes from mammary tissue and liver was measured throughout the course of pregnancy and lactation in Sprague–Dawley rats. Basal constitutive AHH activity in mammary tissue and liver of untreated rats did not change significantly during pregnancy or lactation. In rats injected with beta-naphthoflavone (BNF), AHH activity in liver microsomes increased approximately 25-fold over basal levels and the degree of enzyme induction by BNF was relatively constant throughout pregnancy and lactation. In mammary tissue, however, the induction of AHH by BNF increased dramatically from about 10 times basal at the beginning of pregnancy to over 80 times basal on day 3 of lactation. The high inducibility of mammary AHH during late pregnancy and early lactation exists both when activity is expressed per unit microsomal protein or per unit tissue DNA. Increased inducibility of mammary AHH may contribute to the resistance rats show to hydrocarbon carcinogenesis during pregnancy and lactation. Since the activity of hepatic AHH does not change significantly during pregnancy or lactation, it seems unlikely that resistance is due to altered hepatic metabolism of the hydrocarbons. AHH activity can be associated both with 'metabolic activation' and 'detoxification' of aromatic hydrocarbons. The balance between local 'activation' and 'detoxification' of aromatic hydrocarbons by AHH in mammary tissue during different physiological states is important in determining susceptibility to carcinogenesis and requires further study.