AbstractThe influence of dietary caffeine on the genotoxicity of the cooked food mutagen 2‐amino‐3,8‐dimethylimidazo[4,5‐f]‐quinoxaline (MelQx) was evaluated using the host‐mediated assay in mice. For four weeks, BALBIc mice were fed a purified diet with or without caffeine (0.01% wt/wt in the diet). In the host‐mediated assay, Salmonella typhimurium TA98 was given intravenously immediately before an oral dose of MelQx (1.5 mglkg body wt). After one hour, the mice were killed, the Salmonellae were recovered from the liver, and the number of mutants (his+revertants) were determined. Consumption of caffeine led to a 47% reduction in the number of mutants induced by MelQx (p<0.001). Subsequent in vitro experiments using S. typhimurium TA98 revealed that the capacity of hepatic S‐9 fractions from the caffeine‐fed mice to covert MelQx to an active mutagen was reduced by approximately 35%. This effect was not attributable to caffeine in the S‐9 preparation. These data suggest that consumption of caffeine modifies MelQx mutagenicity by altering the spectrum of enzymes involved in its activation.