INDUCTION OF CYTOCHROMES P-4501A AND P-4502B IN VARIOUS ORGANS OF RATS TREATED WITH HEXACHLOROBENZENE AND AROCHLOR-1254

The activity and content of CYP1A1, CYP1A2, CYP2B1, and CYP2B2(3) in l iver, lungs, and kidneys of Wistar rats treated with mixed-type induce rs (hexachlorobenzene (HCB)(4) and Arochlor 1254 (AR)) and with classi cal inducers, (i.e., phenobarbital (PB) and methylcholanthrene (MC)) w ere studied. Administration of AR and MC noticeably stimulated ethoxyr esorufin (ER)-O-deethylase and methoxyresorufin (MR)-O-demethylase act ivities in all the investigated organs. The effect of HCB on monooxyge nases of lung and kidney was much lower. The pentoxyresorufin (PR)-O-d ealkylase activity in lung and kidney remained unchanged in all the ca ses. Western blot analysis using monoclonal antibodies against CYP1A a nd CYP2B revealed that expression of their genes, triggered by various inducers, was tissue-specific. In fact, in liver MC, AR, and HCB indu ce immunologically-relevant CYP1A1 and CYP1A2. In lung microsomes of t he MC-treated rats only CYP1A1 exists, whereas in those of the AR- or HCB-treated rats both CYP1A1 and CYP1A2 could be detected. In kidney, on administration of AR and HCB, only CYP1A1 was found. These data sug gest that mixed-type inducers cause coordinated synthesis of CYP1A1 an d CYP1A2 in lung which is not characteristic of MC induction. In liver of the PB-treated rats both CYP2B1 and CYP2B2 were detected, whereas in lungs and kidneys only the former was found. Administration of HCB failed to influence materially the induction pattern. Dramatic changes in the expression of the CYP2B genes were provoked by the AR inductio n. In liver and lungs the immunoblot analysis revealed, besides CYP2B1 and CYP2B2, one more protein. Its nature is under consideration. Thus , the results show that induction of various cytochrome P-450s is not only tissue-specific, but also depends on the type of the inducer.