REVERSIBILITY OF PROMOTER INDUCED HEPATIC FOCAL LESION GROWTH IN MICE

The effect of cessation of phenobarbital and dieldrin treatment on hep atic focal lesion growth in male B6C3F1 mice was investigated. Followi ng induction of lesions by diethylnitrosamine, mice were placed on con trol NIH-07 diet (control diet) or NIH-07 diet containing either dield rin (10.0 mg/kg diet) or phenobarbital (500 mg/kg diet). Mice were sac rificed after 30 and 60 days of dietary treatment, Two additional grou ps of mice were fed either the dieldrin-or phenobarbital-containing di et for 30 days followed by feeding of NIH-07-only diet for an addition al 30 days, The effect of treatment and removal of dieldrin or phenoba rbital on lesion growth was examined by measuring both the number of f ocal lesions per liver and the relative volume of focal lesions, In ad dition, the rate of cell proliferation and programmed cell death in fo cal lesion growth was investigated by examining DNA synthesis and apop tosis in the focal lesions, Dietary dieldrin or phenobarbital increase d the number of focal lesions and the focal lesion volume, In both die ldrin- and phenobarbital-treated mice, an increased number of eosinoph ilic lesions were seen. The focal lesion volume was increased in both eosinophilic and basophilic lesions, Dieldrin and phenobarbital treatm ent also increased the DNA synthetic labeling index in both eosinophil ic and basophilic lesions, Removal of dieldrin or phenobarbital from t he diet after 30 days of promoter treatment decreased the total number and volume of hepatic focal lesions. The labeling index of the focal lesions was also decreased in these mice, At the terminal sacrifice, t he percentage of apoptotic cells in focal lesions was higher in mice f ed dieldrin- or phenobarbital-containing diets for the entire 60 days than in mice returned to control diet for the last 30 days. Eosinophil ic lesions were more dependent on the presence of a promoting stimulus than the basophilic lesions, These data indicate that induction acid maintenance of the growth of some preneoplastic lesions in the mouse m ay be dependent upon continuous tumor promoter treatment.