Caffeine inhibition of the metabolic activation of a carcinogen, 4-nitroquinoline-1-oxide, in cultured Chinese hamster cells.

The cytotoxic effect of 4-nitroquinoline-1-oxide (4NQO) on cultured Chinese hamster cells was drastically reduced by the presence of caffeine (0.2-1 mM). Caffeine, however, did not reduce the cytotoxicity of 4-hydroxyaminoquinoline-1-oxide (4HAQO), an active metabolite of 4NQO. The 105 000 g supernatant from the cell homogenate could catalyze the conversion of 4NQO to 4HAQO in the presence of NADPH or NADH as a hydrogen donor. This enzyme activity was strongly inhibited by caffeine (0.1-10 mM) or dicumarol (10(-8)-10(-6) M), an inhibitor of DT diaphorase (E.C.1.6.99.2). Dicumarol also reduced the cytotoxicity of 4NQO. These results clearly suggest that caffeine inhibits the conversion step of 4NQO to 4HAQO, resulting in a decrease in the cytotoxicity of 4NQO. Furthermore, the frequency of 6-thioguanine-resistant mutation by 4NQO was also strongly reduced by the presence of caffeine (1 mM) in cultured Chinese hamster cells, being consistent with the results of cytotoxicity.