The role of dietary aflatoxin in the genesis of hepatocellular cancer in developing countries.
Impaired activity of the liver microsomal mixed-function-oxidase (MFO) system is characteristic of protein malnutrition. It explains the accumulation of aflatoxin (AFB1) in livers of kwashiorkor victims, whose staple foods are usually heavily contaminated with this fungal toxin. Dietary rehabilitation of such children with high-protein foods not only increases the activity of the liver MFO system but also stimulates DNA replication and rapid regeneration of liver cells. Under such circumstances highly reactive metabolites of AFB1, such as the AFB1-epoxide, can produce malignant transformation of the cells by binding covalently with genetic macromolecules. Alternating cycles of food shortage and sufficiency, which usually characterise impoverished communities, and liver-cell hyperplasia stimulated by the non-genetic cytotoxic effects of AFB1 or parasitic infestation promote rapid replication of the transformed cells.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D002648:Child; D003043:Cocarcinogenesis; D004261:DNA Replication / Q000187:drug effects; D003906:Developing Countries; D004044:Dietary Proteins / Q000009:adverse effects; D005506:Food Contamination; D006509:Hepatitis B / Q000150:complications / Q000378:metabolism; D006801:Humans; D007732:Kwashiorkor / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000209:etiology* / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D000096702:Aflatoxin Poisoning
D000348:Aflatoxins; D004044:Dietary Proteins; D016604:Aflatoxin B1; D006899:Mixed Function Oxygenases