Carcinogenesis Advance Access originally published online on March 11, 2004
Carcinogenesis 2004 25(8):1507-1515; doi:10.1093/carcin/bgh137
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Carcinogenesis vol.25 no.8 © Oxford University Press 2004; all rights reserved.
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Both suboptimal and elevated vitamin intake increase intestinal neoplasia and alter crypt fission in the ApcMin/+ mouse
1 Gastroenterology and 2 Histopathology Departments, Imperial College, Hammersmith Hospital, London and 3 Histopathology Unit, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London, UK
4 To whom correspondence should be addressed Email r.goodlad{at}cancer.org.uk
The effects of vitamin deficiency on intestinal cancer are unclear, and even less is known about the consequences of excessive intake. We therefore investigated the actions of altered vitamin content on intestinal polyp development, cell proliferation and crypt fission in a mouse model of neoplasia. Ninety multiple intestinal neoplasia (ApcMin/+) mice and 90 wild-type littermates, 4 weeks old, were divided into six groups and fed either a control semi-synthetic diet, or the semi-synthetic diet with the vitamin content lowered to a third of the RDA or the semi-synthetic diet with the vitamin content increased 5-fold (except for retinol and folate, which were doubled). The number and size of polyps in the small and large intestines were scored after 8 weeks on the diets, as was cell proliferation (native mitoses per crypt) and crypt fission. The small intestines of the low and high vitamin groups were heavier than the controls. There were significantly more polyps and the tumour burden was higher in both the low and the high vitamin groups (P < 0.02). Proliferation was slightly reduced by the vitamin alteration and crypt fission was significantly increased in the ApcMin/+ mice when compared with the wild-type (P < 0.001). Fission indices were decreased by vitamin alteration in the small intestine, and increased in the colon, but only in the ApcMin/+ mice. The effects of vitamin alteration on polyp number were most pronounced in the proximal intestine, which is also the site of maximum crypt fission. Both vitamin deficiency and over-supplementation can markedly enhance polyp number and tumour burden.
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