Effects of sphingomyelin on aberrant colonic crypt foci development, colon crypt cell proliferation and immune function in an aging rat tumor model

Abstract

Sphingomyelin (SPM) was assessed in older rats for in vivo effects on multiple immune responses and the development of colon preneoplastic lesions. Fifty-four-week-old rats were injected with 10 mg/kg body weight of the carcinogen azoxymethane (AOM), and then treated with 35 mg/kg body weight SPM orally for 6 weeks beginning 6 weeks after AOM treatment. None of the immune functions tested (antibody formation, delayed-type hypersensitivity or natural killer cell cytotoxicity) were significantly affected by SPM treatment. Natural killer (NK) cell activity was, however, decreased in all rats that were treated with AOM. There was a tendency for decreased aberrant crypt foci (ACF) numbers in the SPM-treated rats but this reduction was only significant for the largest lesions (>nine crypts per foci). The decreased ACF numbers were most evident in the proximal end of the colon. Colonic crypt cell proliferation was also decreased in SPM treated rats. This reduction was primarily in the base of the crypt column. Also, low numbers of ACF developed spontaneously in rats not treated with AOM, but no ACF were present in non-AOM rats that also received SPM. It appears that SPM may have effects on the post-initiation development of preneoplastic lesions in the rat colon but not on the immune functions assessed in this study.