Natural killer activity in a medium-term multi-organ bioassay for carcinogenesis

Natural killer (NK) cell activity was evaluated after the initiation and pr omotion steps in a medium-term multi-organ bioassay for carcinogenesis. NK cell activity was assessed in vitro by Cr-51 release assay at the 4th and 3 0th weeks of the experiment. Male Wistar rats were sequentially initiated w ith N-diethylnitrosamine (DEN i.p.), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN drinking water), N-methyl-N-nitrosourea (MNU i.p.), dihydroxy-di-N-pro pylnitrosamine (DHPN drinking water) and N,N'-dimethylhydrazine (DMH s.c.) at subcarcinogenic doses for 4 weeks (DMBDD initiation). One group was eval uated at the 4th week and the other was maintained without any further trea tment until the 30th week. Two initiated groups were exposed through the di et to 2-acetylaminofluorene (2-AAF) or phenobarbital (PB), from the 6th unt il the 30th week, Five additional groups were studied to evaluate the effec ts of each initiator on NK activity. All groups submitted to initiation onl y, initiation plus promotion, or promotion only, developed significantly mo re preneoplastic lesions than the untreated control group. The main target organs for tumor development in the initiated animals n ere the liver and t he colon, irrespective of treatment with 2-AAF or PB. NK cell activity was not affected bal exposure to genotoxic carcinogens after initiation, at the 4th week. Treatments only with PB or 2-AAF did not change NK cell activity , However, decreased NK cell activity was registered in the group only init iated with DMBDD and in the group given DMBDD+2-AAF. This late depression o f NK cell activity at the 30th week could be related to the production of s uppressing molecules by the tumor cells.