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John H. Weisburger,¹ Joanne Braley,¹ Joel Reinhardt,¹ Cesar Aliaga,¹ Abraham Rivenson,¹ Gordon C. Hard,¹ Xue-Ming Zhang,² Mami Takahashi,³ Hiroyasu Esumi,³ and Takashi Sugimura³

¹American Health Foundation, Valhalla, New York; ²Ontario Cancer Institute, Toronto, Canada; ³National Cancer Center, Tokyo, Japan

Abstract

The modulation by dietary fat levels of intestine carcinogenesis is well documented. New developments suggest that calcium ions may also play a role. A rapid bioassay, the induction of foci of aberrant crypts in the colon, was used to explore the interaction between dietary fat and calcium. Male F344 rats 6 weeks of age were placed on diets containing 5 or 20% corn oil, and 0.04 or 0.32% calcium ion, as calcium lactate. Each dietary group was fed 400 ppm 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) , and negative controls received the diets alone. A positive control group was given 2 mg N-nitrosomethylurea (NMU) intrarectally four times in a 2-week period. All rats were killed after 9 weeks. The intestinal tract was rinsed with Krebs-Ringer buffer. After staining a 6-cm segment of the descending colon and rectum with 0.2% methylene blue, foci of aberrant crypts were evaluated microscopically. With PhlP as a carcinogen, the rats on a high-fat, low-calcium level had more foci of aberrant crypts than animals on a low-fat level. With the higher calcium level, there were fewer foci and aberrant crypts, but the effect of fat was still significant. With NMU and a low-calcium level, the effect of fat level was evident. However, with the higher calcium intake, there were considerably more foci of aberrant crypts than on the low-calcium level, and the effect of the dietary fat level was not obvious. Thus, with the dietary carcinogen PhlP, an enhancing effect of high fat intake and a protective effect of a higher calcium intake on the induction of intestinal foci of aberrant crypts could be visualized in a 9-week test. With limited intrarectal administration of NMU, the association with dietary fat was evident on a low-calcium intake. On a high-calcium intake, there was a considerably higher number of aberrant crypt foci, perhaps because of the more advanced carcinogenic process with NMU. --Environ Health Perspect 102(Suppl 6) :53-55 (1994)

Key words: food carcinogens, heterocyclic amines, 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhlP) , nutrition and cancer, colon cancer, fat and colon cancer, calcium and colon cander, rapid bioassay