MUTATIONS IN LIVER DNA OF LACI TRANSGENIC MICE (BIG BLUE) FOLLOWING SUBCHRONIC EXPOSURE TO 2-ACETYLAMINOFLUORENE

2-Acetylaminofluorene (2-AAF) was administered at levels of 0, 300 and 600 ppm in the diet for 28 days to female transgenic mice bearing the lacI gene in a lambda vector (Big Blue(R) mice). The lambda vector wa s excised from liver DNA and packaged in vitro into bacteriophage part icles which were allowed to infect E. coli bacteria, forming plaques o n agar plates. Approximately 10(5) plaques were screened per animal fo r the appearance of a blue colour, indicative of mutations in the lacI gene which had resulted in an inactive gene product. Background mutat ion rate was 2.7 X 10(-5) (pooled results of two animals, 8 mutant pla ques/289530 plaques). At 300 ppm in the diet, the rate of 3.5 x 10(-5) (8/236300) was not significantly increased over background. At 600 ppm in the diet, the rate increased approximately 3 fold to 7.7 x 10(-5) (17/221 240). In comparison to the usual single or 5-day carcinogen ex posure regimes, the 4-week exposure protocol allowed the use of much l ower dose levels (10-1000 fold lower). Overt toxicity could thus be av oided. The daily doses used were somewhat higher than those required i n 2-year carcinogenicity studies with 2-AAF.