| Summary: | Human cancer intervention trials have found beta-carotene to be effective in reducing the genotoxic damage to oral mucosa cells that resulted from carcinogen exposure. Design of intervention trials using beta-carotene has so far lacked an important component, knowledge of the accumulation and retention of this putative chemopreventive agent in the tissues of interest. The factors of dose, timing of administration of supplements, and the effects of confounding factors are aspects of trial design that demand an understanding of the kinetics of beta-carotene in human tissues.
The oral mucosa is the only tissue so far that has been investigated for beta-carotene levels in exfoliated cells. A non-invasive technique for sample collection, suitable for sampling populations, in combination with a highly sensitive assay for beta-carotene, is appropriate for use with other epithelial sites that may be targets of intervention trials; one such site is the uro-genital tract.
This thesis describes preliminary investigations towards design of an intervention trial with beta-carotene directed at cells of the uro-genital tract.
Initial studies established the feasibility of measuring beta-carotene in uro-genital tract cells, and verified that the technical variation in the assays of oral mucosa cells and urogenital
tract cells was less than the variation between individuals in the study population.
A short-term (four-day) supplementation trial compared the effects of three doses of beta-carotene, given orally, on the beta-carotene content of exfoliated oral mucosa cells. Ingestion of 360 mg, 180 mg, and 90 mg of beta-carotene resulted in a rise in median cell beta-carotene levels from 1.8, 1.5, and 1.0 ng/10⁶ cells to 9.2, 7.7, and 3.9 ng/10⁶ cells, respectively, one week after the loading. Due to variation in response, the effects of the three doses were not significantly different from one another. The elevation in beta-carotene levels persisted for 2 weeks after the loading. The kinetic profile of the accumulation and retention of beta-carotene in uro-genital tract cells differed markedly from that of oral mucosa cells, in individuals who were supplemented for four weeks with a field trial dosage of beta-carotene. Median beta-carotene levels in uro-genital tract cells of beta-carotene-supplemented individuals increased from 0.6 ng/10⁶ cells to 2.8 ng/10⁶ cells during the loading period, a level significantly higher than that of the placebo group, but declined immediately after the end of the loading to levels that were not significantly elevated. In contrast, beta-carotene in exfoliated oral mucosa cells remained at significantly elevated levels until four weeks after the cessation of loading.
Tissue-specific features of beta-carotene accumulation in response to its administration need to be taken into consideration when designing intervention strategies that use beta-carotene. === Medicine, Faculty of === Pathology and Laboratory Medicine, Department of === Graduate
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