Enhancement of altered hepatic foci in rat liver and inhibition of intercellular communication in vitro by the pyrethroid insecticides fenvalerate, flucythrinate and cypermethrin.
Male Sprague-Dawley rats dosed with N-nitrosodiethylamine (NDEA) 24 h after two-thirds partial hepatectomy were treated with the pyrethroid insecticides fenvalerate, flucythrinate or cypermethrin in the diet for 20 weeks. Altered hepatic foci were analyzed by quantitative stereology from paraffin-embedded sections stained for gamma-glutamyltranspeptidase (GGT) or glutathione S-transferase P (GST-P). The present results demonstrate that the pyrethroids tested all enhance the development of NDEA-initiated, GGT-positive foci in rat liver at non-hepatotoxic doses. On the contrary, the volume fractions of GST-P-positive foci were not elevated as compared to the control group. The three pyrethroids tested all inhibited the transfer of Lucifer Yellow CH between WB-F344 rat liver epithelial cells in culture, supporting the increase of GGT-positive foci and suggesting that these substances can act as tumour promoters. The discrepancy between the results from analyses using GGT or GST-P as markers emphasizes the importance of understanding the mechanism underlying the expression of different markers for preneoplastic lesions and the importance of such effects in tumour promotion.
Hemming
H
H
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Flodström
S
S
Wärngård
L
L
D000818:Animals; D001835:Body Weight; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D005982:Glutathione Transferase / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009570:Nitriles; D009929:Organ Size; D010648:Phenylacetates / Q000633:toxicity*; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D007306:Insecticides; D009570:Nitriles; D010648:Phenylacetates; D011722:Pyrethrins; C017160:cypermethrin; C027975:flucythrinate; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; C017690:fenvalerate