ELEVATED BINDING TO URE PEBP2 DURING THE LATE STAGES OF NNK AND BENZO[ALPHA]PYRENE-INDUCED CARCINOGENESIS IN A/J MICE/

To provide better understanding about the alterations in transcription factor activities during the promotion and progression stages of lung carcinogenesis we have utilized the A/J mice lung tumor model in whic h two potent lung carcinogens, 4-(methyl-nitrosamino)-1-(3-pyridyl)-1- butanone (NNK) and benzol[a]pyrene (BaP), were co-administered. Nuclea r proteins prepared from lung, brain, kidney, liver and colon of the A /J mice, 19 weeks after the last carcinogen administration, as well as from their respective non-treated controls, were tested for their bin ding to polyoma enhancer binding protein 2 (PEBP2) target sequence and UV-responsive element (URE). PEBP2 represents a newly identified fami ly of transcription factors that was shown to play a role in cellular differentiation and transformation. URE is similar to CRE and AP1 targ et sequences, to which the members of ATF/AP1 transcriptional factors family bind. We demonstrate here that there is a marked increase in bi nding to both PEBP2 and URE sequences in lung, liver, kidney and brain of the treated mice. Such binding appears to be dependent on the mode of carcinogen administration as it was better noticed in the intragas tric injected group than in the intraperitoneal group, Taken together, our findings suggest that increased binding to the URE and to PEBP2 t arget sequence reflects changes in transcriptional activities which oc cur at late stages of lung carcinogenesis in a fashion which appear to depend on mode of carcinogen administration.