Carcinogenesis Advance Access published online on August 19, 2005
Carcinogenesis, doi:10.1093/carcin/bgi210
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1 Department of Food Science and Nutrition, 1334 Eckles Ave., University of Minnesota, St. Paul, MN 55108
* To whom correspondence should be addressed. Indole-3-carbinol (I3C) and phenethyl isothiocyanate (PEITC) are breakdown products of the glucosinolates glucobrassicin and gluconasturtiin, respectively, and are thought to reduce carcinogen activation by P450 enzymes. To assess the effects of these compounds on colon cancer risk, rats were divided into 5 groups and fed the following diets: control diet (AIN-93G), or diets with PEITC or I3C added to the control diet: High PEITC (3.37 mmols/kg diet -high level of PEITC), low PEITC (0.67 mmols/kg -low level of PEITC), high I3C (6.8 mmols/kg -high level of I3C), and low I3C (1.36 mmols/kg -low level of I3C). Diets were fed for 2 weeks before and 10 weeks after administration of the colon carcinogen azoxymethane. Precancerous lesion (aberrant crypt foci, ACF) number in the distal colon was significantly lower in both high I3C and low I3C groups (6.9 ± 0.8 and 5.9 ± 0.59 per cm2, respectively) when compared to the control group (10.4 ± 0.9). No significant difference in ACF number was found between either PEITC group and the control group. ACF expressing sialomucin, thought to indicate ACF more likely to progress to tumors, were greater in the high PEITC group (13 ± 3) than the control (5.6 ± 2). Mucin-depleted ACF, suggested to have the greatest tumorigenic potential, tended to be lower in the low I3C group (p<0.06) compared to the control group. Mucosal apoptotic and cell proliferation labeling indices did not differ among groups, suggesting that reduction in ACF number by I3C does not involve alterations in mucosal cell kinetics. No significant differences were found among the groups in hepatic cytochrome P450 2E1 (CYP2E1) activity, the first enzyme involved in activation of azoxymethane. However, there was increased activity of NADPH- and NADH reductases with high I3C, enzymes involved in the transfer of reducing equivalents to cytochrome P450. These results suggest that I3C lowers colon cancer risk through a mechanism not involving reduction of carcinogen activation by CYP2E1.
Received December 20, 2004
Revised August 2, 2005
Accepted August 12, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Effects of indole-3-carbinol and phenethyl isothiocyanate on colon carcinogenesis induced by azoxymethane in rats
Daniel D. Gallaher, E-mail: dgallahe{at}che.umn.edu
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