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

Female Wistar rats were treated sequentially with 4-dimethyl-aminoazobenzene(4-DAB) and N-nitrosodiethanolamine (NDEOL) for periods of 6weeks. One group received first 4-DAB (0.06% in the diet) andNDEOL (2000 p.p.m. in the drinking water) thereafter, whilethe second group was treated in the reversed sequence; controlgroups received the single agent alone. The extent of foci negativefor adenosine-triphosphatase (ATPase) or positive for -glutamyl-transpep-tidase(-GT)-activity was quantitated in liver as a means to assesscarcinogenic efficacy. A very low response was obtained in ratstreated first with 4-DAB and then with NDEOL whereas a strongincrease in number and especially in size of foci was observedwhen 4-DAB was given after NDEOL. The response in this lattergroup was clearly over-additive. Treatment of rats with eithercarcinogen alone resulted in similar pattern of increases inthe volumetric fraction of liver occupied by ATPase-deficientfoci. A differential behaviour, however, was observed with respectto islet size. NDEOL produced large numbers of small foci whereaswith 4-DAB only few foci were obtained which grew rapidly inthe presence of the carcinogen. These findings are consistentwith the hypothesis that 4-DAB, besides acting as an initiator,has very strong promoting activity as was to be expected fromthe characteristic relationship between carcinogen dose andtime of liver tumour induction.