methylazoxymethanol and Intestinal-Neoplasms

The antitumor action of inhibitors of cyclooxygenase (indomethacin) and lipoxygenase activity (nordihydroguaiaretic acid) of arachidonic acid cascade was investigated in the chemically induced large bowel tumors in Sprague-Dawley rats. Indomethacin treatment completely prevented the carcinogenic effect of methylazoxymethanol. Thus, no tumors were found in the 14 rat test group, compared with 13 of 14 tumor-bearing rats in the untreated control group. Although nordihydroguaiaretic acid treatment does not abolish prostaglandin synthesis, it does reduce the effect of the carcinogen and tumors were found in only five of 14 treated rats. From this study it can be postulated that not only is reduction in prostaglandin formation responsible for the inhibition of tumor growth, but also leukotrienes may play some role.

Topics: Animals; Arachidonic Acids; Catechols; Indomethacin; Intestinal Neoplasms; Male; Masoprocol; Methylazoxymethanol Acetate; Prostaglandin Antagonists; Rats; Rats, Inbred Strains

The role of Lactobacillus arabinosus in the malignant transformation of tumors of the large intestine was investigated in mice. Methylazoxymethanol (MAM) acetate, at a weekly dose of 0.2 mg/10 g body weight, was given to germfree mice and to mice monocontaminated with either L. arabinosus or Escherichia coli. At sacrifice, the activity of non-specific esterase, beta-glucuronidase, and alcohol dehydrogenase within the liver and intestine was examined biochemically and histochemically. Non-specific esterase activity in the liver and large intestine was significantly higher in L. arabinosus mice than in the other 2 groups. Also, beta-glucuronidase activity in the large intestine and alcohol dehydrogenase activity in the liver were significantly greater in L. arabinosus mice than in the other groups. Esterase was localized in the mitochondria and absorptive granules within the mucosal epithelium of the large intestine. An apparent increase in the number of certain organelles was observed in the L. arabinosus mice, compared with the other groups. These results suggest that L. arabinosus plays an important role in MAM acetate tumorigenesis and malignant transformation.

Topics: Administration, Oral; Alcohol Dehydrogenase; Alcohol Oxidoreductases; Animals; Azo Compounds; Esterases; Germ-Free Life; Glucuronidase; Intestinal Neoplasms; Intestine, Large; Intestine, Small; Lactobacillus; Liver; Male; Methylazoxymethanol Acetate; Mice; Mice, Inbred ICR; Microscopy, Electron; Neoplasms, Experimental

The influence of diet restriction on induction of intestinal tumors in Sprague-Dawley rats by two unique carcinogenic agents was investigated: methylazoxymethanol acetate [(MAM) CAS: 592-62-1], which requires metabolic activation, and N-methylnitrosourea [(MNU) CAS: 684-93-5], which is a direct-acting carcinogen. Most of the tumors induced by MAM developed in the small intestine and less frequently in the colon, but MNU produced tumors predominantly in the colon. Among rats fed the restricted diet (12 g/day), the production of tumors by MAM was significantly reduced compared to that of counterpart rats on the ad libitum diet. However, dietary restriction did not modify the production of tumors in rats by MNU. The same relationship of diet restriction to tumor induction was demonstrable when MAM and MNU were administered to the same test rats: Numbers of MAM-related tumors, especially in the small intestine, were reduced and numbers of MNU-related tumors in the colon were unchanged. Dietary restriction modified the tumorigenic response of rats to MAM but not to MNU.

Topics: Animals; Body Weight; Colonic Neoplasms; Diet; Intestinal Neoplasms; Intestine, Large; Intestine, Small; Male; Methylazoxymethanol Acetate; Methylnitrosourea; Rats; Rats, Inbred Strains