MUTAGENICITY OF NITROPHENANTHRENE DERIVATIVES FOR SALMONELLA-TYPHIMURIUM - EFFECTS OF NITROREDUCTASE AND ACETYLTRANSFERASE

To determine the mutagenicity of nitrophenanthrenes, three mononitroph enanthrenes (NPhs), 11 dinitrophenanthrenes (diNPhs) and eight trinitr ophenanthrenes (tiNPhs) were synthesized, and their mutagenicity was i nvestigated by using Salmonella typhimurium his - strains TA98, TA100, and TA98NR, nitroreductase-deficient, and TA98/1,8-DNP6, O-acetyltran sferase-deficient mutants, and strains YG1021 and YG1026, nitroreducta se-overproducing mutants of TA98 and TA100, respectively, and strains YG1024 and YG1029, O-acetyltransferase-overproducing mutants of TA98 a nd TA100, respectively. 1-, 3- and 9-NPhs induced 329, 620 and 438 rev ertants per nmol in strain TA100, respectively, and 4,839, 11,309 and 16728 revertants per nmol, respectively, in strain YG1029. Mutagenicit y of 1,6-, 2,6-, 2,9-, 2,10-, 3,5-, 3,6- and 3,10-diNPh was elevated i n strains YG1021, YG1024, YG1026 and YG1029,Among these derivatives, 1 ,6-, 2,6-, 3,6- and 3:10-diNPhs were more mutagenic in strains YG1024 and YG1029 than YG1021 and YG1026, and they showed a structure-activit y relationship between mutagenicity and NO2-substitution. Nitro deriva tives substituted at the 3 and 6 positions of their chemical structure strongly mutated both strains YG1024 and YG1029, whereas those substi tuted at the 9 and 10 positions showed weak mutagenicity. In addition, nitro substituents at positions 4 and 5 were perpendicular while thos e on positions 2,3,6 and 7 were nearly coplanar to the aromatic ring. Furthermore, 2,6,9-, 3,6,9- and 1,6,9-trinitrophenanthrenes (triNPhs) were mutagenic for strain TA100, and their mutagenicity was more enhan ced in YG1024 and YG1029 than in YG1021 and YG1026. Of the eight triNP hs all except 1,5,10-triNP were mutagenic in TA98 and TA100, and their mutagenicity was more enhanced in YG1024 and YG1029 than in YG1021 an d YG1026. These results suggest that these compounds are mutagens that are activated by O-acetyltransferase esterification following nitrore ductase. The nitrated derivatives substituted at the 2(7) and 3(6) pos itions of the phenanthrene ring were highly mutagenic. The relationshi p between chemical structure and the mutagenicity of NPh derivatives i s discussed.