Modification of carcinogenesis by antioxidants and other compounds.
Studies were made on the effects of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium L-ascorbate (SA), ethoxyquin (EQ) and acetaminophen (AAF) on the induction of neoplastic lesions in the liver, kidney or urinary bladder of rats initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN), diethylnitrosamine (DEN) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The number and area of histochemical gamma-glutamyltranspeptidase-positive (gamma-GT+) foci per unit area of liver section in rats given BHA, BHT, EQ or AAP, but not SA, were significantly less than in rats given EHEN or DEN alone. Similarly, the number of hyperplastic nodules (HN) in groups given BHA or AAP and their area in groups given BHA, EQ or AAP were significantly less than in control groups. Induction of hepatocellular carcinoma (HCC) was also clearly inhibited by these three chemicals. In contrast, the incidence and quantitative values of preneoplastic lesions and renal cell adenoma in the group given EHEN were significantly increased in groups given BHA, EQ or AAP administration. For assesing the influence of BHA and BHT on urinary bladder carcinogenesis, rats received BHA or BHT after treatment with BBN. The incidences and the number per unit length of basement membrane of papilloma and carcinomas were significantly increased in rats given BHA. BHT also showed significant increase but values were less than with BHA. These results clearly demonstrated that BHA, BHT, EQ and AAP inhibit the development of gamma-GT+ foci, or HN and HCC, whereas BHA, EQ and AAP enhance the appearance of preneoplastic and neoplastic lesions in the kidney, BHA and BHT also enhancing urinary bladder carcinogenesis.
D000082:Acetaminophen / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002273:Carcinogens / Q000037:antagonists & inhibitors*; D004052:Diethylnitrosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D005015:Ethoxyquin / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000139:chemically induced; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000975:Antioxidants; D002273:Carcinogens; C023845:N-ethyl-N-hydroxyethylnitrosamine; D002083:Butylated Hydroxyanisole; D000082:Acetaminophen; D004052:Diethylnitrosamine; D005015:Ethoxyquin; D005723:gamma-Glutamyltransferase