DIFFERENT PATTERNS OF DNA REPLICATION INHIBITION BY BENZO(A)PYRENE AND 3-METHYLCHOLANTHRENE IN MAMMALIAN CELLS IN VITRO.

Abstract

TWO METABOLIC ACTIVATION SYSTEMS, EXEMPLI GRATIA S15 FRACTION AND MOUSE EMBRYONIC FIBROBLAST (MEF) FEEDER LAYER, HAVE BEEN SHOWN TO HAVE EFFECTS ON THE PATTERN CHANGE OF BENZO(A)PYRENE (BP)- AND 3-METHYLCHOLANTHRENE (MC)-INDUCED DNA REPLICATION INHIBITION. THE PRESENT STUDIES WERE PERFORMED IN ORDER TO ELUCIDATE THE MECHANISM OF SUCH EFFECTS IN CHINESE HAMSTER OVARY CELLS (CHO-K1) USING ALKALINE SUCROSE GRADIENT SEDIMENTATION ANALYSIS. WHEN CHO-K1 CELLS WERE TREATED WITH BP IN THE ABSENCE OF METABOLIC ACTIVATION SYSTEM, INHIBITION OF REPLICON INITIATION AND CHAIN ELONGATION WAS OBSERVED AT 12 HR AND AT 24 HR, RESPECTIVELY, REGARDLESS OF THE DOSE, EVEN THOUGH THE LEVEL OF THE OVERALL REPLICATION INHIBITION WAS VERY LOW. HOWEVER, WHEN THESE CELLS WERE TREATED WITH BP OR MC IN THE PRESENCE OF THE S15 FRACTION FOR 1 HR, THE RATE OF DNA SYNTHESIS WAS GREATLY DECREASED. AT LOW DOSES BELOW 10(-6) M WHEREAS THE CHAIN ELONGATION WAS MARKEDLY INTERRUPTED AT 10(-4) M. THESE RESULTS SUGGEST THAT THE PATTERN OF DNA REPLICATION INHIBITION INDUCED BY MC OR BP COULD BE INFLUENCED TO A GREATER DEGREE BY THE CHOICE OF METABOLIC ACTIVATION SYSTEM EMPLOYED THAN BY THE DOSE OR THE DURATION OF EXPOSURE.