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© 1984 Oxford University Press

other

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

Michael Schwarz, Dale Pearson, Rüdiger Port and Werner Kunz

Institute of Biochemistry, German Cancer Research Centre Im Neuenheimer Feld 280, D-6900 Heidelberg, FRG

Female Wistar rats were treated sequentially with 4-dimethyl-aminoazobenzene (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-transpep-tidase ({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.


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