IN-VIVO ANTIMUTAGENIC ACTIVITY OF BETA-CAROTENE IN RAT SPLEEN LYMPHOCYTES

The anticarcinogenic effects of beta-carotene (BC) have been extensive ly investigated, but only in vitro assays have examined the ability of BC to modulate gene mutation, In view of the current interest in the provitamin as a cancer chemopreventive agent, and the association betw een mutagenesis and carcinogenesis, we have dosed Fischer 344 rats wit h the model carcinogen N-ethyl-N-nitrosourea (ENU) and investigated th e relationships among BC intake, its tissue accumulation, and antimuta gen activity, Animals received drinking water supplemented with BC at doses of 0-0.25% ad libitum, using three dosing schedules, In one grou p BC dosing commenced before, and continued for three alternating week s after i.p. injection of 100 mg ENU/kg; another group was given BC on ly after mutagen treatment, Animals from the first two groups were sac rificed 5 weeks post-mutagen treatment, and cells were isolated from t he spleen to determine the frequency of 6-thioguanine-resistant (6-TG( r)) T-lymphocytes. The presence of BC caused a reduction in the freque ncy of 6-TG(r) T-cells produced by ENU, but the inhibition was non-lin ear within the range of BC doses used, BC intake only after mutagen tr eatment was more effective than the combination of pre- and post-mutag en intake, In the third group, rats were treated with 100 mg ENU/kg, a nd BC administration was continued at a fixed dose of 0.15% in the dri nking water for 2, 4, 6, or 8 weeks, Measurement of the frequency of 6 -TG(r) T-cells at the end of the specified times showed >50% reduction in ENU-mediated mutagenicity throughout the experiment, Analysis of B C levels in the liver and in the spleen following BC intake before and during mutagen exposure revealed higher levels than when BC was given only after mutagen treatment, Continuous intake of BC also showed inc reased tissue levels, There were some correlations observed between BC tissue levels and the antimutagenic effects for the first two groups, but these correlations were not statistically significant, possibly d ue to the small numbers of animals used, Taken together, the results d emonstrate that intact BC is absorbed, stored, and exerted antimutagen ic effects against a chemical carcinogen in rats without first being t ransformed to retinol in the gastrointestinal tract.