Background:

Azoxymethane is a colon carcinogen which leads to the formation of DNA adducts.

Azoxymethane is a colon carcinogen which leads to the formation of DNA adducts. On an equal protein basis, hepatic microsomes are much more active than SI and colon microsomes in NADPH-dependent Azoxymethane bioactivation and N7-mG adduct formation. Hepatic microsomes show the highest activity in the hydroxylation of Azoxymethane, followed by SI and colon microsomes[1].

Regardless of the strain, the amounts of O6-mG and N7-mG produced by Azoxymethane are highest in the liver, followed by proximal and distal colons, which have similar levels, and then by duodenum, jejunum and ileum. Results indicate that the Azoxymethane-induced DNA adduct formation in the SI and colon does not depend on bioactivation by hepatic P450 enzymes. Irrespective of the mouse strain, no aberrant crypt foci (ACF) is detected in the colons of saline-treated mice; in contrast, colonic ACF is detected in all three strains of Azoxymethane-treated mice[1]. The Azoxymethane-treated athymic mice have approximately an 11-fold lower tumor incidence than similarly treated WT animals[2].

[1]. Megaraj V, et al. Role of hepatic and intestinal p450 enzymes in the metabolic activation of the colon carcinogen azoxymethane in mice. Chem Res Toxicol. 2014 Apr 21;27(4):656-62. [2]. Whetstone RD, et al. Colon carcinogenesis in wild type and immune compromised mice after treatment with azoxymethane, and azoxymethane with dextran sodium sulfate. Mol Carcinog. 2016 Jul;55(7):1187-95.