Influence of the herbicide Linuron on growth rate and gap-junctional intercellular communication of cultured endothelial cells.
On the basis of in vivo toxicological long-term tests performed on rodents, the herbicide Linuron [3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea] has been classified by the U.S. Environmental Protection Agency (EPA) (1988) as a class C carcinogen (possibly carcinogenic to humans). However, when Linuron was analyzed for genotoxicity, negative results were obtained. An epigenetic, tumor-promoting potential was hence suspected to be responsible for the oncogenic activity of the molecule. In the absence of in vivo data concerning the tumor-promoting activity of the herbicide and being well established that tumor promoters interfere with the cell growth rate and gap-junctional permeability, the effects of technical grade Linuron and of its trade formulation (Linuron 50) on these parameters were investigated. This is especially important in the case of the formulated preparation for a correct estimate of the health hazard to humans. Cytotoxicity and gap-junctional intercellular communication (GJIC) assays were performed on the endothelial cell line F-BAE GM 7373, an in vitro cell system known to be responsive to the biological effects of tumor promoters. A time- and dose-related cytotoxic effect was found for both Linuron and Linuron 50, the latter being the far more cytotoxic of the two. However, when tested at noncytotoxic concentrations over a period of 48 h, neither Linuron nor Linuron 50 altered the capacity of F-BAE GM 7373 cells to intercommunicate. On the basis of the results obtained, the possibility that Linuron and Linuron 50 are endowed with tumor-promoting activity is discussed. In vivo studies on tumor-promoting and genotoxic activity are in progress to complement the information available on the toxicological properties of Linuron and its trade preparation.
Mazzoleni
G
G
Unit of General Pathology and Immunology, School of Medicine, University of Brescia, Italy.
Telò
P
P
Camplani
A
A
Tanganelli
S
S
Monarca
S
S
Ragnotti
G
G
D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D017629:Gap Junctions / Q000187:drug effects*; D006128:Growth / Q000187:drug effects; D006801:Humans; D008044:Linuron / Q000633:toxicity*
D008044:Linuron