Azoxymethane, as a colon carcinogen, can lead to the formation of DNA adducts[1]. Azoxymethane (AOM) causes O(6)-methylguanine adduct formation which leads to G-->A transitions[2].
In vivo, 7-week-old conventional male C57BL/6 mice were injected intraperitoneally with 6 doses of 10 mg/kg AOM, feces from obese individuals promote colorectal cancer formation in AOM-treated CRC mouse model[3]. SWR/J, A/J mice was treated with 10 mg/kg AOM i.p. once a week for 8 weeks developed tumors, with a distribution that was limited to the distal colon[4]. In wild-type (WT) mice, AOM treatment (10 mg/kg) induced a 2.5-fold increase in intestinal crypt stem cell survival. WT mice receiving AOM exhibited increased intestinal apoptosis and a simultaneous reduction in crypt mitotic figures within 8 h of injection[5].
[1] Chen W, et al. Effect of tea on the formation of DNA adducts by azoxymethane. Xenobiotica. 1998 Feb;28(2):213-7.
[2] Wali RK, et al. Inhibition of O(6)-methylguanine-DNA methyltransferase increases azoxymethane-induced colonic tumors in rats. Carcinogenesis. 1999 Dec;20(12):2355-60.
[3] Kang X, et al. Altered gut microbiota of obesity subjects promotes colorectal carcinogenesis in mice. EBioMedicine. 2023 Jul;93:104670.
[4] Papanikolaou A, et al. Azoxymethane-induced colon tumors and aberrant crypt foci in mice of different genetic susceptibility. Cancer Lett. 1998 Aug 14;130(1-2):29-34.
[5] Riehl TE, et al. Azoxymethane protects intestinal stem cells and reduces crypt epithelial mitosis through a COX-1-dependent mechanism. Am J Physiol Gastrointest Liver Physiol. 2006 Dec;291(6):G1062-70.
References:
偶氮甲烷作为一种结肠致癌物,可导致DNA加合物的形成[1]。偶氮甲烷(AOM)导致O(6)-甲基鸟嘌呤加合物的形成,从而导致G->A跃迁[2]。
在体内,7周龄的常规雄性C57BL/6小鼠腹膜内注射6剂量的10 mg/kg AOM,来自肥胖个体的粪便促进AOM治疗的CRC小鼠模型中结直肠癌癌症的形成[3]。SWR/J,A/J小鼠用10 mg/kg AOM腹腔注射治疗,每周一次,持续8周,出现肿瘤,其分布仅限于远端结肠[4]。在野生型(WT)小鼠中,AOM处理(10 mg/kg)诱导肠隐窝干细胞存活率增加2.5倍。接受AOM的WT小鼠在注射后8小时内表现出肠细胞凋亡增加和隐窝有丝分裂图同时减少[5]。