Protease inhibitor suppression of colon and anal gland carcinogenesis induced by dimethylhydrazine.
In the present study, we examined the ability of chymostatin, a highly specific inhibitor of chymotrypsin, to suppress dimethylhydrazine-induced colon carcinogenesis, and the dose-response relationship for an extract of soybeans containing the Bowman-Birk inhibitor (BBI) to suppress dimethylhydrazine-induced colon carcinogenesis, when added to the diet of mice. Our results showed that: (i) diets containing 0.1% BBI reduced the incidence of adenocarcinomas of the colon approximately 50%, but had no effect on the incidence of squamous cell carcinomas of the anal gland; (ii) the suppressive effect requires protease inhibitor activity, as the autoclaved BBI, in which all protease inhibitory activity has been destroyed, was ineffective at suppressing the incidence of adenocarcinomas; (iii) chymostatin suppressed the incidence of squamous cell carcinomas of the anal gland, but not adenocarcinomas of the colon; and (iv) the growth rates of the animals were the same in each of the experimental groups. Our results indicate that the levels of anticarcinogenic protease inhibitors present in the diets of these animals do not have any adverse effects on the growth or general health of the animals.
Billings
P C
PC
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Newberne
P M
PM
Kennedy
A R
AR
D000818:Animals; D001005:Anus Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004127:Dimethylhydrazines; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D004127:Dimethylhydrazines; D009842:Oligopeptides; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D014361:Trypsin Inhibitors; C002101:chymostatin