Metabolic activation, meat mutagens

Several mechanisms may contribute to the association of meat with colon cancer. The heterocyclic amines and polycyclic aromatic hydrocarbons present in cooked meat are metabolized, in the body, to mutagens that may condense with DNA to form adducts. If the adduct occurs at a vital base, and if the adduct is not promptly repaired, cancer may result. Another possible mechanism is related to the enhanced excretion of bile salts into the intestines that occurs with a high-fat diet. In brief, the increased amount of bile salts (with a high-fat diet) that reaches the large intestines is metabolized by the gut microflora to an increased amount of modified bile salts. Specifically, lithocholic acid and deoxycholic acid are formed. These modified bile salts are thought to contribute to the conversion of a normal gut cell to a cancer cell. Recent studies suggest that chronic exposure of gut cells to these modified bile salts may result in chronic activation of protein kinase C and chronic... 

Most importantly, one would like to know whether human tissue is capable of producing mutagenic metabolites from the cooked meat fractions. We analyzed the ability of six human liver microsomal preparations to metabolize the basic fraction from the fried meat (Felton et al. 1981b). These preparations, which were all autopsy specimens, were more active than the uninduced mouse or rat liver microsomal fractions. Microsomes from one individual were nearly as active as those from Aroclor-induced rats and mice. The human metabolism appears to be due to primarly cytochrome P-448 activation since alpha-napthoflavone showed a dose dependent inhibition of the production of the mutagenic intermediates (Felton et al., 1981b). This finding not... 

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