P11 Catalytic activity, genotype of detoxifying enzymes and DNA-adducts in human placenta as risk factors for newborns

Abstract

Induction of isozymes of drug-metabolizing enzymes by butylated hydroxytoluene (BHT) was studied in the male ddY mouse and Chinese hamster. In mice given 0.05% BHT in the diet for 14 days cytochrome P-450 contents and the activities of uridine diphosphate-glucuronyl transferase (UDP-GT) and pentoxyresorufin O-dealkylase were markedly increased, while in those fed 0.15% BHT testoterone 6α-, 16α- and 16β-hydroxylases were greatly increased, while indicated induction of cytochrome P-450 isozymes of the CYP2B family. Western blot analysis also showed and increased level of the isozyme immunorelated to rat CYP2B2 by BHT feeding. The activities of aryl hydrocarbon hydroxylase, ethoxycoumarin O-deethylase (ECOD), erythromycin N-demethylase and glutathione S-transferase (GST) remained unchanged. In Chinese hamster given 0.05 and 0.15% BHT in the diet for 14 days activities if ECOD and GST were induced, but cytochrome P-450 contents and the activities of other enzymes were unaffected. Testosterone 15α-hydroxylase was induced in hamster fed 0.15% BHT. These findings suggested that BHT administration in the hamster induced CYP2A2-type isozyme, which was confirmed by Western blot analysis. BHT treatment enhanced activation of benzo[a] pyrene (B[a]P) as determined by the mutagenicity test, especially in Chinese hamster. The results suggest that BHT treatment induces specific isozymes of drug-metabolizing enzymes and might modify the expression of toxicities of other chemicals.