The proliferative effect of dietary butylated hydroxyanisole on methylazoxymethanol treated colonic mucosa

Abstract

Pulse [ 3H] TdR labeling of CF 1 mice fed butylated hydroxyanisole (BHA, 5 g/kg), given 6 injections of methylazoxymethanol (MAM), and examined 1 week later revealed reduction of colonic epithelial cell proliferation compared with rodents not fed BHA (labeling index (LI) 8.8 ± 2.7 vs. 11.4 ± 1.7). Dietary BHA did not prevent extension of the proliferative compartment to the upper third of crypts in MAM treated mice but did restrain the percentage of DNA synthesis shifted to the middle and upper third of the glands (18.5% vs. 26.4%). The mean distribution of the highest labeled cell in BHA was 12 cell positions below that seen in the MAM treated animals with no dietary BHA (position 14 vs. 26) indicating the ability of BHA to contain the size of the proliferative compartment. The accumulated differences between MAM treated groups based on LI along the entire length of the crypts revealed 85% greater activity in the mice not receiving BHA supplementation. Markedly reduced epithelial cell proliferation acts to interfere with the emergence of transmissable neoplastic mutations while containment of the proliferative compartment and restriction of the upward shift of DNA synthesizing cells inhibits adenomatous tumor formation known to appear in the upper regions of the crypts.