MULTIPLE ACTIVATION OF CHLOROFORM IN KIDNEY MICROSOMES FROM MALE AND FEMALE DBA 2J MICE/

Microsomes from the renal cortex of DBA/2J mice can metabolize chlorof orm through oxidative and reductive pathways, similar to hepatic micro somes. The oxidative or reductive nature of CHCl3 activation is strict ly dependent on the oxygenation of the incubation mixture, as indicate d by the formation of qualitatively different adducts to phospholipids (PLs). The protein and lipid binding levels measured in kidney micros omes from control females differed significantly from the binding leve ls observed with kidney microsomes from male and testosterone-treated female DBA/2J mice in aerobic conditions only. Therefore, the sex-depe ndent CHCl3-induced acute nephrotoxicity seems related only with the o xidative CHCl3 activation. The levels of adducts to PL polar heads and to protein showed a strict correlation with each other. Therefore, th e assay of adducts to PL polar heads may be used as a substitute for t he assay of adducts to protein. This might be especially convenient wh en studying the effects of both phosgene and the trichloromethyl radic als.