Paraquat causes S-phase arrest of rat liver and lung cells in vivo.
We examined the in vivo effect of paraquat on the cell cycle in rat liver and lung tissues and the protective effect of tungsten (a xanthine oxidase inhibitor) on paraquat toxicity. The bromodeoxyuridine/propidium iodide double-staining method and flow cytometry were used for cell cycle assessment. Wistar rats were fed a standard diet or a tungsten-enriched diet were injected intravenously with 20 mg/kg paraquat, while uninjected rats served as controls. At 1, 3, and 5 days after paraquat injection, the liver and lungs were removed for examination following in vivo labeling with 20 mg/kg bromodeoxyuridine for 1 h. Liver and lung cells were isolated and incubated with an anti-bromodeoxyuridine antibody and with propidium iodide for DNA staining. Flow cytometry showed that the S-phase cell populations in the liver and lungs of paraquat-injected rats fed a standard diet were increased markedly on days 1 and 3 after injection compared with the control levels. However, on day 5 the liver cells had nearly returned to normal, while the S-phase population remained high in the lungs. In contrast, the S-phase cell populations of liver and lung tissue showed no increase after paraquat injection in rats fed a tungsten-enriched diet. These findings suggest that paraquat-induced cytotoxicity is more prolonged in the lungs than in the liver. In addition, paraquat toxicity appears to be mediated by xanthine oxidase and xanthine oxidase inhibitors may be useful an an antidote.
Matsubara
M
M
Department of Emergency and Critical Care Medicine, Kansai Medical University, Osaka, Japan.
Yamagami
K
K
Kitazawa
Y
Y
Kawamoto
K
K
Tanaka
T
T
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004336:Drug Antagonism; D005434:Flow Cytometry; D006540:Herbicides / Q000633:toxicity*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008297:Male; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D016196:S Phase / Q000187:drug effects*; D017973:Tungsten Compounds / Q000494:pharmacology
D006540:Herbicides; D017973:Tungsten Compounds; C025399:sodium tungstate(VI); D010269:Paraquat