In vitro Activation and Resultant Binding of Benzo[a]pyrene to DNA by Microsomes from Rats Fed Corn and Menhaden Oils

Abstract

Dietary unsaturated fat is required for maximum induction of the hepatic mixed function oxidases (MFO) responsible for activating carcinogens to forms that may bind covalently to DNA. The aim of this study was to assess the influence of dietary fat type and content on the activities of some enzymes involved in activation and detoxification of the carcinogen benzo[a]pyrene (B[a]P). Modification of these changes by pretreatment with phenobarbital (PB) was also evaluated. Male rats were fed diet devoid of fat or containing 20% corn oil (CO) or 20% menhaden fish oil (MO) for 4 days. PB induced soluble glutathione S-transferase, a detoxifying enzyme, only in rats fed dietary fats. Microsomes from rats fed both types of dietary fat had increased levels of cytochrome P-450 (P-450) and PB induced P-450 only in rats fed these fats. Although ethoxycoumarin O-dealkylase was significantly elevated in the MO group, the induction by PB was not dependent on dietary fat type or level. Dietary fat increased microsome-catalyzed in vitro binding of [³H]-B[a]P to calf thymus DNA, especially in response to PB. Menhaden oil depressed B[a]P hydroxylation and PB treatment depressed this activity to the greatest extent in rats fed this diet. When calculated as B[a]P metabolized per unit of P-450, PB seems to induce a P-450 in fat fed animals having lower affinity and capacity for B[a]P hydroxylation and activation than in rats fed the fat-free diet.

Phenobarbital Depression of Hepatic Microsomal Benzo[a]pyrene Hydroxylation in Rats Starved and Refed a Diet Containing Menhaden Fish Oil: Substrate and Fat Level Dependency

“…Also no PEinduced depression was evident in corn-oilfed rats at B[a]P concentrations above 0.24 [i.M (data not shown). This explains our re sults reported earlier that PB decreased B[a]P hydroxylase activity of microsomes of rats fed 20% menhaden oil but not 20% corn oil when measured in incubation mixtures containing a B[a]P concentration of 15 \iM [27].…”