Assay of Linuron and a Pesticide Mixture Commonly Found in the Italian Diet, for Promoting Activity in Rat Liver Carcinogenesis

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Abstract
The herbicide linuron and a mixture of 15 pesticides commonly found in the Italian diet have been assayed for promoting activity in rat liver carcinogenesis. Composition of the pesticide mixture was: benomyl (19.55%); dithiocarbamates (20.67%); thiabendazole (14.94%); diphenylamine (14.25%); chlorthalonil (13.13%); procymidone (7.96%); fenarimol (1.95%); chlorpropham (0.70%); vinchlozolin (0.28%); methidathion (2.37%); chlorpyriphos-ethyl (2.09%); parathionmethyl (1.00%); chlorfenvinphos (0.27%); parathion (0.70%); pyrimiphos-ethyl (0.14%). To determine promoting activity we evaluated induction of preneoplastic foci in diethylnitrosamine-initiated hepatocytes, by positive gammaglutamyl-transpeptidase (GGTase) staining in liver slides, and peroxisome proliferation by peroxisomal-dependent catalase and palmitoyl-CoA-oxidase dosage. For the assay, groups of male Sprague-Dawley rats were initiated with 100 mg/kg diethylnitrosamine intraperitoneally and, one week later, given 150 mg/kg/day linuron or 10 mg/kg/day pesticide mixture, administered by gavage three days a week. All rats were 2/3 hepatectomized at the beginning of the 3rd week. All treatments were terminated at the end of the 8th week, and the rats were sacrificed one week later. No significant increases in number and area (mm2) per slide unit area (cm2) of GGTase-positive foci could be observed in linuron-treated rats (5.84 +/- 1.62/cm2; 0.139 +/- 0.041 mm2/cm2) with respect to controls only initiated with diethylnitrosamine (4.47 +/- 1.30/cm2; 0.182 +/- 0.078 mm2/cm2). After treatment with the pesticide mixture, the number of preneoplastic foci was instead significantly increased (6.91 +/- 2.05/cm2) although the area was not (0.188 +/- 0.128 mm2/cm2). Moreover, no increases in the peroxisome proliferation enzymatic markers were observed in either treated groups. The results imply a possible carcinogenic risk for the population stemming from promoting activities of pesticide mixtures.

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