Hosokawa_1994_Drug.Metab.Dispos_22_889

The ability of di(2-ethylhexyl)phthalate (DEHP), a very widely used commercial plasticizer, to induce hepatic microsomal carboxylesterase isozymes in rats, mice (C5BL/6 and DBA/2 strains), and hamsters was studied by measuring hydrolase activities and by immunoblotting analysis using specific antibodies. Animals were given 2% (v/w) DEHP in the diet for 7 days. In rats, p-nitrophenyl acetate, isocarboxazid, and butanilicaine hydrolase activities and the contents of RL1, RL2, and RH1 in liver microsomes were all increased, but acetanilide hydrolase activity was not increased. In hamsters, the only significant change was a slight increase of butanilicaine hydrolase activity. In mice, butanilicaine hydrolase was strongly induced in both the C57BL/6 (7.35-fold) and DBA/2 (4.96-fold) strains. The anti-RL1 and RH1 antibody-reactive proteins in C57BL/6 mouse liver microsomes were increased, but the extent of induction was much less than that of butanilicaine hydrolase activity. The butanilicaine hydrolysis seems to be catalyzed by not only anti-RL1 reactive protein, but also some other carboxylesterase in C57BL/6 mouse. Anti-RL1 antibody inhibited the DEHP-induced butanilicaine hydrolase activity by > 50%. The results strongly suggest that multiple carboxylesterase isozymes were induced in mouse hepatic microsomes by dietary exposure to DEHP.