Open AccessInhibition of Development of N, N′ ‐Dimethylhydrazine‐induced Rat Colonic Aberrant Crypt Foci by Pre, Post and Simultaneous Treatments with 24 R ,25‐Dihydroxyvitamin D 3
Author(s) -
Salim Elsayed I.,
Wanibuchi Hideki,
Taniyama Tetsuhide,
Yano Yoshihisa,
Morimura Keiichirou,
Yamamoto Shinji,
Otani Shuzo,
Nishizawa Yoshiki,
Morii Hirotoshi,
Fukushima Shoji
Publication year - 1997
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1997.tb00329.x
Subject(s) - aberrant crypt foci , 1,2 dimethylhydrazine , crypt , medicine , dimethylhydrazine , endocrinology , carcinogenesis , metabolite , immunohistochemistry , anticarcinogen , vitamin , vitamin d and neurology , cholecalciferol , chemistry , colorectal cancer , colonic disease , cancer
It has recently been reported that new vitamin D 3 derivatives can exert inhibitory effects on colon carcinogenesis in rats. In the present study the chemopreventive potential of 24 R ,25‐dihydroxyvitamin D 3 (24ff,25(OH) 2 vitainin D 3 ) was assessed in a murine model of colon carcinogenesis. In experiment 1, male 6‐week‐old F344 rats were administered N 2 N ‐dimethylhydrazme (DMH) 20 mg/kg s.c. once a week 4 times. The rats were fed 24 R ,25(OH) 2 vitaniin D 3 at 10 ppm in the diet prior to (pre), together with (simultaneous) or after (post) DMH treatment. Modifying effects were assessed using aberrant crypt foci (ACF), putative preneoplastic lesions, as the end point markers in this model of colon carcinogenesis. After 8 weeks, pre and more markedly simultaneous administration of 24 R ,25‐(OH) 2 vitamin D 3 was found to have reduced the total numbers of ACF and significantly inhibited the development of foci. After 16 weeks, numbers of foci with ≥4 crypts, which are more likely to progress to tumors, were significantly reduced. The most pronounced inhibition of ACF development was noted in rats fed the 24 R ,25(OH) 2 vitaniin D 3 after DMH administration. The reduction was particularly marked in the proximal colon. Blood levels of calcium were not significantly increased over the control levels in groups administered DMH and the vitamin. Immunohistochemical staining showed numbers of proliferating cell nuclear antigen‐positive cells to.be lower in the colonic epithelia of rats fed the vitamin D 3 metabolite than in the controls. In experiment 2, the effect of 24 R ,25‐(OH) 2 vitamin D 3 on the alterations in c‐fos, c‐myc and c‐jun oncogene expression in response to DMH administration was examined by northern blot analysis. The early increase in expression of ornithine decarboxylase (ODC) activity was not altered by 24 R ,25(OH) 2 vitamin D 3 . The results suggest that 24 R ,25(OH) 2 vitamin D 3 is a cancer chemopreventive agent which may suppresses DMH induction of lesions and their subsequent development via an antiproliferative action.