Effect of beta-carotene supplementation on indices of colonic cell proliferation.

BACKGROUND

Epidemiologic studies have shown that consuming foods containing beta-carotene is associated with a decreased incidence of colon cancer. The validity of this association has recently been questioned. It is not known if the rate of colonic cell proliferation differs among individuals with or without a history of colonic polyps or cancer and if proliferation changes in response to beta-carotene.

PURPOSE

This study was intended to (a) determine whether differences exist in colonic cell proliferation in individuals with and without prior colonic polyps or tumors, (b) demonstrate that beta-carotene accumulates in colonic mucosa following dietary supplementation, and (c) determine whether mucosal beta-carotene accumulation influences colonic cell proliferation.

METHODS

Subjects were enrolled in the phase I study from June 1991 until February 1994. The participants included 20 individuals (11 males and nine females, aged 62.3 +/- 8.9 years [means +/- SD]) with normal colons (as judged by recent colonoscopy), 40 (24 males and 16 females, aged 59.6 +/- 10.1 years) with a history of colonic polyp(s), and 41 (30 males and 11 females, aged 67.2 +/- 9.7 years) with prior colon cancer. The subjects in the last two groups consumed either 30 mg of beta-carotene or placebo each morning for 3 months. This dose of beta-carotene has no known toxic effects, but it can increase the serum level by approximately 10-fold. beta-carotene concentration in serum and colonic tissue was quantitated by high-pressure liquid chromatography in samples collected before and after supplementation with beta-carotene or placebo. Cellular proliferation was assessed on the basis of tissue ornithine decarboxylase activity, urinary polyamine excretion, and proliferating cell nuclear antigen expression. The differences in colonic cell proliferation parameters due to beta-carotene supplementation, within and among different groups, were evaluated by the Wilcoxon matched-pairs signed ranked test and the Mann-Whitney test, respectively. All statistical tests were two-sided.

RESULTS

Colonic cell proliferation did not differ in samples obtained from individuals with and without prior colonic polyp(s) or cancer. beta-carotene concentrations in serum and colonic tissue were significantly increased in groups receiving beta-carotene (P < .001). However, cell proliferation did not differ, as judged by any of the three measures, among samples from all experimental groups collected before and after supplementation with beta-carotene.

CONCLUSIONS

Dietary supplementation with beta-carotene for a period of 3 months does not alter colonic cell proliferation in individuals with a history of colonic polyps or cancer.

IMPLICATIONS

The mechanism by which beta-carotene might reduce colon cancer incidence does not appear to involve or result in a change in cell proliferation in the normal colonic mucosa as studied in individuals with a history of colonic polyps or cancer.