ASSAY OF LINURON AND A PESTICIDE MIXTURE COMMONLY FOUND IN THE ITALIAN DIET, FOR PROMOTING ACTIVITY IN RAT-LIVER CARCINOGENESIS

The herbicide linuron and a mixture of 15 pesticides commonly found in the Italian diet have been assayed for promoting activity in rat live r carcinogenesis. Composition of the pesticide mixture was: benomyl (1 9.55%); dithiocarbamates (20.67%); thiabendazole (14.94%); diphenylami ne (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%), chlorfenvinph os (0.27%); parathion (0.70%); pyrimiphos-ethyl (0.14%). To determine promoting activity we evaluated induction of preneoplastic foci in die thylnitrosamine-initiated hepatocytes, by positive gammaglutamyl-trans peptidase (GGTase) staining in liver slides, and peroxisome proliferat ion by peroxisomal-dependent catalase and palmitoyl-CoA-oxidase dosage . For the assay, groups of male Sprague-Dawley rats were initiated wit h 100 mg/kg diethylnitrosamine intraperitoneally and, one week later, given 150 mg/kg/day linuron or 10 mg/kg/day pesticide mixture, adminis tered by gavage three days a week. All rats were 2/3 hepatectomized at the beginning of the ard week. All treatments were terminated at the end of the 8th week, and the rats were sacrificed one week later. No s ignificant increases in number and area (mm(2)) per slide unit area (c m(2)) of GGTase-positive foci could be observed in linuron-treated rat s (5.84+/-1.62/cm(2); 0.139+/-0.041 mm(2)/cm(2)) with respect to contr ols only initiated with diethylnitrosamine (4.47+/-1.30/cm(2); 0.182+/ -0.078 mm(2)/cm(2)). After treatment with the pesticide mixture, the n umber of preneoplastic foci was instead significantly increased (6.91/-2.05/cm(2)) although the area was not (0.188+/-0.128 mm(2)/cm(2)). M oreover, no increases in the peroxisome proliferation enzymatic marker s were observed in either treated groups. The results imply a possible carcinogenic risk for the population stemming from promoting activiti es of pesticide mixtures.