Genotoxicity evaluation of selenium sulfide in in vivo and in vivo/in vitro micronucleus and chromosome aberration assays.
Selenium monosulfide (SeS) was reported to be carcinogenic to livers of male and female rats and livers and lungs of female mice. However, its genotoxicity profile in short-term assays is somewhat equivocal. A multiple endpoint/multiple tissue approach to short-term genetic toxicity testing has been developed in our laboratory. In the present paper, the effect of SeS in in vivo and in vivo/in vitro micronucleus and chromosome aberration assays in rat bone marrow and spleen are reported. In the in vivo assay, small but statistically significant increases in bone marrow micronucleated polychromatic erythrocytes (MNPCEs) were observed 24 h after treatment of rats with 50 mg/kg SeS and 48 h after treatment with 12.5 mg/kg. A significant decrease in the PCE/total erythrocyte (TE) ratio, indicative of cytotoxicity, was observed at the 50 mg/kg dose at the 24-h timepoint. In spleen, no increases in MNPCEs or decreases in the PCE/TE ratios were observed. No evidence of a significant increase in aberrations was observed in bone marrow or spleen. In the in vivo/in vitro assay, no increase in micronucleated binucleated cells or cells with aberrations was observed in SeS-treated rats. The small but statistically significant increases in MN observed in the in vivo study are considered likely not to be biologically significant since no dose-response was observed and all the values obtained were within historical control range in our laboratory. Given the overall genetic toxicity profile of SeS, it appears that SeS may be a weak mutagen and that differences between testing protocols may be very important in determining whether or not it is found to be negative or positive. Histological evidence was obtained in this study that suggests that the liver is the acute target organ of SeS in rats. Given the fact that SeS is selectively hepatocarcinogenic, we are currently testing the hypothesis that the genotoxicity of SeS in rats may be more readily detectable in liver than in bone marrow or spleen.
Moore
F R
FR
Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan 48105, USA.
Urda
G A
GA
Krishna
G
G
Theiss
J C
JC
D000284:Administration, Oral; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D018036:Selenium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects
D009153:Mutagens; D018036:Selenium Compounds; C025698:selenium disulfide