Genetic tests in mice of caffeine alone and in combination with mutagens

Abstract

The possible mutagenicity of caffeine has been studied in mice by the dominant-lethal method, in three experiments. (I) Male mice were given caffeine in drinking water for 8 weeks at 3.6, 13.4, 49, and 122 mg/kg/day (comparable to human consumption of 2.8–95 cups of coffee per day). Subsequent mating of each of six males from each group to five females per week for 8 weeks showed no significant increase in dominantlethal mutations (embryonic deaths) whether expressed as early deaths per pregnant female or as mutation index. Although males consuming the two higher levels of caffeine produced fewer pregnancies, litter sizes of females giving birth were not reduced. (II) Single ip injections of caffeine (15 mg/kg) were given to groups of male mice prior to, subsequent to, and immediately at the time of receiving X-rays (100 r). Each of five males from each group was mated to five females per week for 7 weeks. Embryonic deaths did not show any enhancing effect of caffeine on the mutagenicity produced by the irradiation. (III) Three groups of male mice ingested caffeine in water for 16 weeks at levels of 0, 4 and 13 mg/kg/day. Subgroups of five from each group were given either: no further treatment, a single dose of triethylene melamine at 0.2 mg/kg, or 100 r of X-ray, and mated for 7 weeks as above. Fertility and litter size were not affected by the caffeine pretreatment, nor did it modify the induction of dominant-lethal mutations by triethylene melamine or X-rays. Litter sizes showed no significant preimplantation losses in any experiment. Thus, under the conditions described herein and at the doses employed (higher than human exposure), there was no evidence for the mutagenicity of caffeine or the inhibition of DNA repair mechanisms in these mammalian systems.