Abstract
Caffeine is metabolized by primary rat hepatocytes in culture to metabolites similar to those found in rats in vivo, including 6-amino-5-[ N-formylmethylamino]-1,3-dimethyluracil, one of the major caffeine metabolites produced in the rat. At a substrate-limiting level of caffeine, the rat hepatocytes metabolized 25–30% of the total added caffeine in 24 h. About 99% of the metabolites was found in the extracellular medium and rinse fractions, suggesting that on a volume basis, caffeine metabolites are in equilibrium inside and outside the cells. No detectable caffeine metabolites were produced in preparations of either Chinese hamster V79 cells, or normal human fibroblasts at caffeine concentrations from 5 μM to 5 mM. These results suggest that the varied biological effects induced by caffeine in Chinese hamster cells cannot be attributed to caffeine metabolites and further that the differential responses of Chinese hamster cells and normal human fibroblasts to caffeine are not due to qualitative or quantitative differences in caffeine metabolism in the two cell lines.
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