A 35-year-old male living in a southern region of Africa presents with increasing abdominal pain and jaundice. He has worked as a farmer for many years, and sometimes his grain has become moldy. Physical examination reveals a large mass involving the right side of his liver, and a biopsy specimen from this mass confirms the diagnosis of liver cancer (hepatocellular carcinoma). The pathogenesis of this tumor involves which of the following substances?
Many chemicals are associated with an increased incidence of malignancy. These substances are called chemical carcinogens. Aflatoxin B1, a natural product of the fungus Aspergillus flavus, is metabolized to an epoxide. The fungus can grow on improperly stored peanuts and grains and is associated with the high incidence of hepatocellular carcinoma in some areas of Africa and the Far East. Hepatitis B virus is also highly associated with liver cancer in these regions. direct-acting chemical carcinogens, such as the direct-acting alkylating agents that are used in chemotherapy, most organic carcinogens first require conversion to a more reactive compound. Polycyclic aromatic hydrocarbons, aromatic amines, and azo dyes must be metabolized by cytochrome P450-dependent mixedfunction oxidases to active metabolites.Azo dyes, such as butter yellow and scarlet red, are metabolized to active compounds that have induced hepatocellular cancer in rats, but no human cases have been repoed Vinyl chloride is metabolized to an epoxide and is associated with angiosarcoma of the liver, not hepatocellular carcinoma Reference: Robbins & Cotran Pathologic Basis of Disease, 9edition.
Direct-acting alkylating agents
Aflatoxin B1
Azo dyes
Vinyl chloride
miscellaneous