Inhibition by acetaminophen of intestinal cancer in rats induced by an aromatic amine similar to food mutagens.
The widely used analgesic acetaminophen (APAP) was studied in rats for its ability to inhibit intestinal carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB), which was selected as the carcinogen because of its similarity to the heterocyclic amines formed during cooking and which are postulated to be involved in colon cancer in humans. APAP was fed to male F344 rats at 250 ppm, which is about 1/4 the human therapeutic dose and at 5000 ppm, which is about fivefold the human dose. DMAB was injected subcutaneously at 50 mg/kg body weight weekly for 20 weeks, to assure identical exposures to all animals, followed by 22 weeks of maintenance. The DMAB was an effective inducer of tumours in the small and large intestines, producing an average of 1.3 tumours per animal. Feeding of APAP began 2 weeks before DMAB administration and continued for 44 weeks. A 9% reduction in the number of colon tumours per rat cancer at the low dose and an 86% reduction at the high dose were found. Small intestinal tumour incidence was reduced at both doses. The number of multiple intestinal tumours per rat was reduced by 27% and 49% for the low and high doses, respectively. The dimensions of these neoplasms, especially those in the colon, were also reduced in both dose groups. Thus, APAP, even at a sub-therapeutic dose, inhibited intestinal carcinogenesis induced by DMAB. This allows us to speculate that the effects of low exposures to dietary carcinogens of the heterocyclic amine type could be inhibited by therapeutic doses of APAP.
Williams
G M
GM
American Health Foundation, Valhalla, New York 10595, USA.
Iatropoulos
M J
MJ
D000082:Acetaminophen / Q000008:administration & dosage*; D000611:Aminobiphenyl Compounds; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D000818:Animals; D002273:Carcinogens / Q000037:antagonists & inhibitors*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005506:Food Contamination; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D007420:Intestine, Large / Q000187:drug effects / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D008297:Male; D009153:Mutagens / Q000494:pharmacology*; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D011916:Rats, Inbred F344; D015996:Survival Rate
D000611:Aminobiphenyl Compounds; D018712:Analgesics, Non-Narcotic; D002273:Carcinogens; D009153:Mutagens; D000082:Acetaminophen