In vivo antimutagenic activity of beta-carotene in rat spleen lymphocytes.
The anticarcinogenic effects of beta-carotene (BC) have been extensively 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 between mutagenesis and carcinogenesis, we have dosed Fischer 344 rats with model carcinogen N-ethyl-N-nitrosourea (ENU) and investigated the relationships among BC intake, its tissue accumulation, and antimutagen activity. Animals received drinking water supplemented with BC at doses of 0-0.25% ad libitum, using three dosing schedules. In one group BC dosing commenced before, and continued for three alternating weeks after i.p. injection of 100 mg ENU/kg; another group was given BC only after mutagen treatment. Animals from the first two groups were sacrificed 5 weeks post-mutagen treatment, and cells were isolated from the spleen to determine the frequency of 6-thioguanine- resistant (6-TGr) T-lymphocytes. The presence of BC caused a reduction in the frequency of 6-TGr T-cells produced by ENU, but the inhibition was non-linear within the range of BC doses used. BC intake only after mutagen treatment was more effective than the combination of pre- and post-mutagen intake. In the third group, rats were treated with 100 mg ENU/kg, and BC administration was continued at a fixed dose of 0.15% in the drinking water for 2, 4, 6, or 8 weeks. Measurement of the frequency of 6-TGr T-cells at the end of the specified times showed > 50% reduction in ENU-mediated mutagenicity throughout the experiment. Analysis of BC 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 increased 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 due to the small numbers of animals used. Taken together, the results demonstrate that intact BC is absorbed, stored, and exerted antimutagenic effects against a chemical carcinogen in rats without first being transformed to retinol in the gastrointestinal tract.
Aidoo
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Food and Drug Administration, Division of Genetic Toxicology Jefferson, AR 72079, USA.
Lyn-Cook
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Lensing
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Bishop
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ME
Wamer
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D000818:Animals; D016587:Antimutagenic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002338:Carotenoids / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005038:Ethylnitrosourea; D008099:Liver / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009153:Mutagens; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000187:drug effects* / Q000378:metabolism; D014018:Tissue Distribution; D019207:beta Carotene
D016587:Antimutagenic Agents; D009153:Mutagens; D019207:beta Carotene; D002338:Carotenoids; D005038:Ethylnitrosourea