Promoting effect of 4-dimethylaminoazobenzene on enzyme altered foci induced in rat liver by N-nitrosodiethanolamine.
Female Wistar rats were treated sequentially with 4-dimethylaminoazobenzene (4-DAB) and N-nitrosodiethanolamine ( NDEOL ) for periods of 6 weeks. One group received first 4-DAB (0.06% in the diet) and NDEOL (2000 p.p.m. in the drinking water) thereafter, while the second group was treated in the reversed sequence; control groups received the single agent alone. The extent of foci negative for adenosine-triphosphatase (ATPase) or positive for gamma-glutamyl-transpeptidase (gamma-GT)-activity was quantitated in liver as a means to assess carcinogenic efficacy. A very low response was obtained in rats treated first with 4-DAB and then with NDEOL whereas a strong increase in number and especially in size of foci was observed when 4-DAB was given after NDEOL . The response in this latter group was clearly over-additive. Treatment of rats with either carcinogen alone resulted in similar pattern of increases in the volumetric fraction of liver occupied by ATPase-deficient foci. A differential behaviour, however, was observed with respect to islet size. NDEOL produced large numbers of small foci whereas with 4-DAB only few foci were obtained which grew rapidly in the presence of the carcinogen. These findings are consistent with the hypothesis that 4-DAB, besides acting as an initiator, has very strong promoting activity as was to be expected from the characteristic relationship between carcinogen dose and time of liver tumour induction.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004052:Diethylnitrosamine / Q000031:analogs & derivatives / Q000633:toxicity*; D004357:Drug Synergism; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000378:metabolism; D004124:p-Dimethylaminoazobenzene / Q000633:toxicity*
D002273:Carcinogens; D009602:Nitrosamines; C014129:N-nitrosodiethanolamine; D004052:Diethylnitrosamine; D004124:p-Dimethylaminoazobenzene; D005723:gamma-Glutamyltransferase; D000251:Adenosine Triphosphatases