title: Microbial carcinogenic toxins and dietary anti-cancer protectants.
abstract: Several toxins are known which account for the ability of some bacteria to initiate or promote carcinogenesis. These ideas are summarised and evidence is discussed for more specific mechanisms involving chymotrypsin and the bacterial chymotryptic enzyme subtilisin. Subtilisin and Bacillus subtilis are present in the gut and environment and both are used commercially in agriculture, livestock rearing and meat processing. The enzymes deplete cells of tumour suppressors such as deleted in colorectal cancer (DCC) and neogenin, so their potential presence in the food chain might represent an important link between diet and cancer. Over-eating increases secretion of chymotrypsin which is absorbed from the gut and could contribute to several forms of cancer linked to obesity. Inhibition of these serine proteases by Bowman-Birk inhibitors in fruit and vegetables could account for some of the protective effects of a plant-rich diet. These interactions represent previously unknown non-genetic mechanisms for the modification of tumour suppressor proteins and provide a plausible explanation contributing to both the pro-oncogenic effects of meat products and the protective activity of a plant-rich diet. The data suggest that changes to farming husbandry and food processing methods to remove these sources of extrinsic proteases might significantly reduce the incidence of several cancers.
authors.affiliation: College of Medical, Veterinary and Life Sciences, University of Glasgow, West Medical Building, Glasgow, G12 8QQ, UK. Trevor.Stone@glasgow.ac.uk.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Stone
authors.affiliation: Department of General Internal Medicine, Ashtead Hospital, Ashtead, Surrey, KT21 2SB, UK.
authors.forename: L Gail
authors.initials: LG
authors.lastname: Darlington
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001419:Bacteria / Q000378:metabolism*; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism*; D004032:Diet; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D014118:Toxins, Biological / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014118:Toxins, Biological
keywords: Cancer; DCC; Dependence receptors; Diet; Microbiome; Serine proteases