Statistical analysis of a carcinogen mixture experiment. I. Liver carcinogens.
This paper describes factorial experiments designed to determine whether 2 liver carcinogens act synergistically to produce liver cancers in Fischer 344 rats. Four hepatocarcinogens, cycad flour, lasiocarpine (CAS: 303-34-4), aflatoxin B1 (CAS: 1162-65-8), and dipentylnitrosamine (CAS: 13256-06-9), were studied in pairwise combinations. Each of the 6 possible pairs was studied by means of 4 X 4 factorial experiment, each agent being fed at zero and at 3 non-zero doses. Methods of analysis designed explicitly for this study were derived to study interaction. These methods were supplemented by standard statistical methods appropriate for one-at-a-time studies. Antagonism was not discovered in any chemical mixture. Some chemical mixtures did interact synergistically. Findings for male and female animals were generally, but not always, in agreement.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity; D000818:Animals; D001391:Azo Compounds / Q000633:toxicity*; D002273:Carcinogens / Q000008:administration & dosage*; D003492:Cycasin / Q000633:toxicity*; D004357:Drug Synergism; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D013223:Statistics as Topic
D000348:Aflatoxins; D001391:Azo Compounds; D002273:Carcinogens; D009602:Nitrosamines; D011763:Pyrrolizidine Alkaloids; C032849:N,N-diamylnitrosamine; D003492:Cycasin; D016604:Aflatoxin B1; C005136:lasiocarpine