SELECTIVE DIELDRIN PROMOTION OF HEPATIC FOCAL LESIONS IN MICE

Chronic exposure to a number of chlorinated pesticides, including diel drin, results in an increased incidence and/or multiplicity of hepatoc ellular neoplasia in mice, with no such effect in similarly treated ra ts. One possible explanation of this observed selective carcinogenicit y is species-specific hepatic tumor promotion. In the present study we examined the dose-response effect of dieldrin (at several doses) on f ocal lesion growth (tumor promotion), hepatocyte apoptosis and DNA syn thesis in rat and mouse liver, Preneoplastic focal hepatic lesions wer e produced by diethylnitrosamine (DEN). After the lesions developed, m ice and rats were placed into one of the following dose groups: contro l (NIH-07 diet) or 0.1, 1.0 or 10.0 mg dieldrin/kg diet. Increased foc al lesion volume, number of foci per liver and focal DNA synthetic lab eling index were observed in 10 mg dieldrin/kg diet-treated mice, but not in similarly treated rats. Dieldrin at dietary concentrations of 0 .1 and 1.0 mg/kg diet produced an increase in the number of preneoplas tic lesions (0.1 mg/kg diet at 7 days only) and focal volume (0.1 mg/k g diet at 7 and 30 days, 1.0 mg/kg diet at 30 days), but these concent rations did not increase focal DNA labeling index. At dietary concentr ations of 0.1, 1.0 and 10 mg dieldrin/kg diet no significant change in lesion percent volume, number of preneoplastic lesions per liver or p reneoplastic lesion DNA labeling index was seen in treated rats compar ed with control rats, Apoptosis, a form of programed cell death, was n ot decreased in foci by any concentration of dieldrin in either rats o r mice. Thus our results suggest that dieldrin may function as a mouse -specific tumor promoter through increased lesion DNA synthesis.