THE EFFECT OF DIETHYLHEXYL ADIPATE (DEHA) ON CYTOCHROME P-450 (P-450) IN NONPREGNANT (NP) AND PREGNANT (P) MICE

Abstract

DEHA, a chemical used in plastic food wrap and cosmetics, causes intrauterine growth retardation and fetal abnormalities in rats, decreases fertility in mice and is a hepatocarcinogen. Since changes in P-450 activity can alter both carcinogenic and teratogenic activity, we studied the effect of DEHA on hepatic P-450 in P and NP C57BL/6J mice using aminopyrine-N-demethylase activity (APD), P-450 content and HPLC isozyme pattern in non-treated (NT) and treated (T) females. Mice were treated with 1 intraperitoneal injection of DEHA (12.5 ml/kg body weight) 48 hrs before preparation at hepatic microsomes.

In NP mice, DEHA increased P-450 content (NT = 0.80 ± 0.11, T = 1.11 ± 0.05 nmoles/mg protein p< 0.001) but did not alter APD activity, (NT = 14.7 ± 1.9, T = 16.3 ± 5.3 nmoles HCHO/min/mg protein). In P mice treated on day 15 of gestation, DEHA increased both P-450 (NT = 0.67 ± 0.06, T = 0.92 ± 0.12 nmoles/mg protein, p< 0.001) and APD (NT = 7.0 ± 0.1, T = 14.0 ± 2.8 nmoles HCHO/min/mg protein p<0.001). HPLC elution patterns confirmed DEHA induction of P-450 constitutive isozymes and demonstrated that P-450-gest, an isozyme induced in mouse pregnancy (Biochem Pharm, in press), was decreased by DEHA treatment.

In conclusion. DEHA increased P-450 content in NP and P mice but increased APD only in P mice. In the P mouse, DEHA decreased P-450-gest but increased other P-450 isozymes. Future studies are needed to determine if the reproductive effects of DEHA are mediated through changes in P-450 isozymes.