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2132263 
Technical Report 
Structural Requirements Favoring Mutagenic Activity among Methylated Pyrenes in S. Typhimurium 
Rice, JE; Geddie, NG; Defloria, MC; Lavoie, EJ 
1988 
NIOSH/00179097 
A Decade of Progress 
A Decade of Progress 
The mutagenic activity of a series of monomethyl and dimethylpyrenes was assessed in cultured Salmonella-typhimurium cells. An S9 mix prepared from rat liver homogenate was used for metabolism studies and the mutagenicity assay; assays performed with metabolic activation contained 200 microliters of the S9 mix per plate. Mutagenicity of the methylpyrenes was evaluated by the average number of histidine revertant colonies. Pyrene (129000), 1-methylpyrene (2381217), 2-methylpyrene (3442782), and 4-methylpyrene (3353126) were not mutagenic in the absence of S9 mix; 1-methylpyrene was mutagenic in the presence of S9 mix. While none of the dimethylpyrenes exhibited any direct acting mutagenic activity, 1,3-dimethylpyrene and 1,6-dimethylpyrene were the most potent mutagens in the presence of S9 mix; maximum mutagenic response was obtained at a dose of 50 micrograms per plate. The presence of a methyl group at a peri/position adjacent to each K-region resulted in greatly enhanced mutagenic activity among the tested methylpyrenes. High performance liquid chromatography of the metabolites of 1-methylpyrene was performed to explore the decreased mutagenic activity of 1-methylpyrene as compared to 1,3-dimethylpyrene or 1,6-dimethylpyrene; results suggested that an arene oxide adjacent to a peri/methyl substituent exhibited enhanced mutagenic activity as compared to an epoxide which was not similarly located; the synthesized 9,10-oxide of 1-methylpyrene was nearly twice as mutagenic as the 4,5-oxide at a dose of 5 micrograms per plate.