Expression data from NRK-52E cells treated with monuron for 6h, 24h and 72h and rats exposed to monuron for 72h.

Monuron (1,1-dimethyl-3-(4-chlorophenyl) urea) is a non-selective phenylurea herbicide, widely used in the developing countries, however concerns have been raised about it toxicity and carcinogenicity. Monuron was evaluated by the National Toxicology Program (1988) and shown to be a male rat-specific renal carcinogen; however the mechanism of carcinogenesis is unknown. In this study we have examined the effect of sub-cytotoxic exposure to monuron (250µM) at 6h, 24h and 72h on the whole-genome expression profile in a rat proximal renal tubule cell line (NRK-52E). In addition we examined the short term exposure of MON in kidney and liver of exposed rats. We used microarrays to detail the mechanism of toxicity and possibly carcinogenicity of monuron. NRK-52E cells were cultured to confluence on 6-well plates. Cells were then exposed to chlorothalonil dissolved in DMSO (0.1%) at the IC10 concentration at 72h (1.1 μM CHL) or DMSO only as control. After 6h, 24h and 72h the medium was removed and RNA was extracted from the cells. Three studies were conducted at each time point. Eight Wistar-derived rats where bred in the Life Science Support Unit at Liverpool John Moores University male rats (190-240g) 7-9 weeks of age were used in this study. Four rats being dosed with MON at 40mg/kg body weight on day 1 and 400mg/kg body weight on days 2 and 3, at 5ml/kg in corn oil. Four control animals were dosed with corn oil at 5ml/kg. Seventy two hours after the last dose all rats were killed by a rising concentration of carbon dioxide, the liver and kidneys quickly removed and immersed in RNAlater.