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Carcinogenesis Advance Access originally published online on November 18, 2004
Carcinogenesis 2005 26(2):387-393; doi:10.1093/carcin/bgh331
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Carcinogenesis vol.26 no.2 © Oxford University Press 2005; all rights reserved.

ARTICLE

Green vegetables, red meat and colon cancer: chlorophyll prevents the cytotoxic and hyperproliferative effects of haem in rat colon

Johan de Vogel1,–3, Denise S.M.L. Jonker-Termont1,2, Esther M.M. van Lieshout1,2, Martijn B. Katan1,3 and Roelof van der Meer1,2,*

1 Nutrition and Health Programme, Wageningen Centre for Food Sciences (WCFS) and 2 NIZO Food Research, PO Box 20, 6710 BA Ede, The Netherlands and 3 Wageningen University, Bomenweg 2, 6703 HD Wageningen, The Netherlands

* To whom correspondence should be addressed at: WCFS/NIZO Food Research, Kernhemseweg 2, PO Box 20, 6710 BA Ede, The Netherlands. Tel: +31 318 659559; Fax: +31 318 650400; Email: roelof.van.der.meer{at}nizo.nl

Diets high in red meat and low in green vegetables are associated with increased colon cancer risk. This association might be partly due to the haem content of red meat. In rats, dietary haem is metabolized in the gut to a cytotoxic factor that increases colonic cytotoxicity and epithelial proliferation. Green vegetables contain chlorophyll, a magnesium porphyrin structurally analogous to haem. We studied whether green vegetables inhibit the unfavourable colonic effects of haem. First, rats were fed a purified control diet or purified diets supplemented with 0.5 mmol haem/kg, spinach (chlorophyll concentration 1.2 mmol/kg) or haem plus spinach (n = 8/group) for 14 days. In a second experiment we also studied a group that received haem plus purified chlorophyll (1.2 mmol/kg). Cytotoxicity of faecal water was determined with a bioassay and colonic epithelial cell proliferation was quantified in vivo by [methyl-3H]thymidine incorporation into newly synthesized DNA. Exfoliation of colonocytes was measured as the amount of rat DNA in faeces. In both studies haem increased cytotoxicity of the colonic contents ~8-fold and proliferation of the colonocytes almost 2-fold. Spinach or an equimolar amount of chlorophyll supplement in the haem diet inhibited these haem effects completely. Haem clearly inhibited exfoliation of colonocytes, an effect counteracted by spinach and chlorophyll. Finally, size exclusion chromatography showed that chlorophyll prevented formation of the cytotoxic haem metabolite. We conclude that green vegetables may decrease colon cancer risk because chlorophyll prevents the detrimental, cytotoxic and hyperproliferative colonic effects of dietary haem.


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