Promoting effect of 4-dimethylaminoazobenzene on enzyme altered foci induced in rat liver by N-nitrosodiethanolamine

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Abstract
Female Wistar rats were treated sequentially with 4-dimethylaminoazobenzene (4-DAB) and N-nitrosodiethanolamine (NDEOL) for periods of 6 wk. One group received first 4-DAB (0.06% in the diet) and NDEOL (2000 ppm in the drinking water) thereafter, while the 2nd group was treated in the reversed sequence; control groups received the single agent alone. The extent of foci negative for 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 behavior, however, was observed with respect to islet size. NDEOL produced large numbers of foci whereas with 4-DAB only few foci were obtained which grew rapidly in the presence of the carcinogen. 4-DAB, besides acting as an initiator, apparenly has very strong promoting activity as to be expected from the characteristic relationship between carcinogen dose and time of liver tumor induction.