Effects of dietary conjugated linoleic acid on DNA adduct formation of PhIP and IQ after bolus administration to female F344 rats

Meats cooked at high temperatures contain mutagenic heterocyclic amines suc h as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-m ethylimidazo[4,5-f]quinoline (Ie). In female Fischer 344 rats, IQ is a mult iorgan carcinogen, whereas PhIP induces mammary adenocarcinomas. For IQ and PhIP, N-hydroxylation, catalyzed by microsomal cytochrome P-450 1A1 and/or 1A2, and then esterification, especially O-acetylation, are the principal steps leading to DNA adduct formation. Conjugated linoleic acid (CLA) is a mixture of conjugated linoleic acid isomers found in various meat and dairy products. We have examined the effect of dietary CLA on DNA adduct formati on by PhIP and Ie in female Fischer 344 rats. Four-week-old animals were ma intained on AIN-76A diet without or with CLA (4% wt/wt) and treated with IQ or PhIP (50 mg/kg by gavage) after two weeks. Animals were killed (4/group ) one, four, and eight days later. DNA isolated from mammary epithelial cel ls, liver, colon, and white blood cells was analyzed for carcinogen-DNA add ucts by P-32-postlabeling assays. On Day I, dietary CLA significantly inhib ited adduct formation (82.0%) in mammary epithelial cells in IQ-but not in PhIP-treated rats. In the colon, dietary CLA significantly inhibited PhIP-D NA adduct formation (18.7%) on Day 8 but increased IQ-DNA adduct formation (30.5%) on Day 8. Dietary CLA had no effect on adduct levels in liver or wh ite blood cells. Calf thymus DNA was incubated with N-hydroxy-PhIP or -IQ i n the presence of acetyl-CoA. Enzymatic activation was catalyzed by liver o r mammary cytosol. A two-week pretreatment with 2% (wt/wt) dietary CLA had no effect on O-acetyltransferase-catalyzed IQ- or PhIP-DNA adduct formation . It is concluded, under certain conditions, that dietary CLA can lower IQ- and PhIP-DNA adduct formation. Overall, however, the major mode of action of CLA is probably by a mechanism other than the inhibition of the N-hydrox ylation and subsequent O-acetylation of PhIP or IQ.