Carcinogenic effect of arsenate in C57BL/6J/Han mice and its modulation by different dietary selenium status.
In this study, carcinogenic effects of arsenate in female C57BL/6J/Han mice exposed in drinking water to 50, 200 or 500microgAs/L for 24 months were investigated. All animals were fed low-selenium diet, however half of them were supplemented with sodium selenite in drinking water (200microgSe/L) to ensure the normal dietary level of selenium. Glutathione peroxidase activity in erythrocytes and plasma as well as selenium concentration in plasma after 3, 6, 12 and 18 months in satellite groups showed considerable decrease in animals from non-selenium supplemented groups in comparison to supplemented groups. A clear arsenic concentration-dependent increase in the number of malignant lymphoma associated with increase in the risk of death was observed (hazard ratio=0.91, 1.46, and 2.24, for 50, 200 and 500microgAs/L, respectively). No significant influence of selenium dietary status on arsenic carcinogenicity was shown. A significant association between selenium supplementation status and increased risk of death of the animals from causes other than malignant tumors was found (HR=1.79, p=0.04).
Stepnik
Maciej
M
Nofer Institute of Occupational Medicine, 8 Sw. Teresy Street, 91-348 Łódź, Poland. mstep@imp.lodz.pl
Stetkiewicz
Jan
J
Krajnow
Aleksander
A
Domeradzka
Katarzyna
K
Gradecka-Meesters
Dobrosława
D
Arkusz
Joanna
J
Stańczyk
Małgorzata
M
Palus
Jadwiga
J
Dziubałtowska
Elzbieta
E
Sobala
Wojciech
W
Gromadzińska
Jolanta
J
Wasowicz
Wojciech
W
Rydzyński
Konrad
K
D000818:Animals; D001149:Arsenates / Q000378:metabolism / Q000633:toxicity*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D004032:Diet; D004326:Drinking; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D008223:Lymphoma / Q000139:chemically induced; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009374:Neoplasms, Experimental / Q000139:chemically induced; D012643:Selenium / Q000097:blood / Q000494:pharmacology*; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*
D001149:Arsenates; D002273:Carcinogens; D014874:Water Pollutants, Chemical; D005979:Glutathione Peroxidase; D012643:Selenium; C025657:arsenic acid