NEIL1 protects against aflatoxin-induced hepatocellular carcinoma in mice

• DOI: 10.1073/pnas.1620932114
• Publication Date: 2017-04-04T00:43:34Z
• Authors: Vladimir Vartanian; Irina G. Minko; Supawadee Chawant...; Patricia A. Egner; Ying-Chih Lin; Lauriel F. Earley; Rosemary Makar; Jennifer R. Eng; Matthew T. Camp; Liang Li; Michael P. Stone; Michael R. Lasarev; John D. Groopman; Robert G. Croy; John M. Essigmann; Amanda K. McCullough; R. Stephen Lloyd
• Keywords: Male; Mice, Knockout; 0301 basic medicine; Carcinoma, Hepatocellular; Protective Agents; Poisons; DNA Glycosylases; 3. Good health; Mice, Inbred C57BL; DNA Adducts; Mice; 03 medical and health sciences; Liver Neoplasms, Experimental; Aflatoxins; Animals; Female

Significance Human dietary exposures to aflatoxin in some of the most populated and underdeveloped portions of the world are a major contributing factor to the formation of human hepatocellular carcinomas (HCCs) that account for over 700,000 deaths annually. Although the genomic signatures for aflatoxin-driven carcinogenesis are G:C to T:A point mutations arising from bypass of aflatoxin-induced DNA adducts, maintenance of genome stability has been generally attributed to nucleotide excision repair. However, we present three lines of evidence that the DNA base excision repair pathway initiated by the DNA glycosylase NEIL1 is the major contributor in maintaining genomic stability following aflatoxin exposures. These findings suggest that inactivating NEIL1 polymorphic variants in the human population could affect susceptibility to aflatoxin-induced HCC.