BP metabolism and the in vivo binding to hepatic DNA of rats fed diets containing menhaden fish oil.

Abstract

It is well established that dietary polyunsaturated omega-6 fatty acids promote tumorigenesis and support the activity of mixed-function oxidases (MFO), which are responsible for carcinogen activation. This study was undertaken to determine if increased levels of dietary menhaden fish oil (rich in omega-3 fatty acids) would affect in vivo binding of [3H]benzo[a]pyrene (BP) to rat liver DNA. The effects of dietary menhaden oil on the activities of phase I and phase II drug-metabolizing enzymes were also studied to determine the possible relationships between the activity of these enzymes and the binding of [3H]BP metabolites to liver DNA. Following a single intraperitoneal injection of [3H]BP, more BP was bound to liver DNA recovered from rats fed diet containing 20% menhaden oil for 11 days at all time intervals tested (16, 24, 48, and 192 hours) than was bound from rats fed 0.5% menhaden oil. The increased binding of [3H]BP to liver DNA of rats fed the high level of menhaden oil may be due, in part, to increases in the MFO responsible for BP activation (as suggested by increased cytochrome P-450 level and total BP hydroxylase activity). The higher concentrations of radioactivity extracted from blood of rats fed 20% menhaden oil diet at the initial time periods (16 and 24 hours) may be a reflection of the greater capacity of the liver to metabolize BP to more water-soluble metabolites. The maximum velocity (Vmax) for ethoxycoumarin O-dealkylase, expressed as nanomoles per milligram protein or per gram liver, was increased three- to fourfold by feeding the high level of menhaden oil. The differences in these enzymatic responses suggest that certain form(s) of cytochrome P-450 are preferentially increased by feeding the omega-3 fatty acids of menhaden oil.