title: Comutagenic and coclastogenic effects of selenium in vitro and in vivo.
abstract: The comutagenic activity of selenium was investigated using in vitro and in vivo techniques, including the liquid suspension modification of the standard Salmonella/microsome mutagenicity assay, the metaphase analysis of chromosome aberrations in CHO cells and in mouse bone marrow as well as the micronucleus assay in mouse bone marrow. 4 h growth of S. typhimurium TA1535 in a nutrient broth containing 2.9 x 10(-5) M but not 1.16 x 10(-5) M Na2SeO3 caused an up to 10-fold increase of the number of N-methylnitrosourea (MNU, 2.0-2.5 mM)-induced his+ revertants and an up to 2-fold elevation of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 1.48 x 10(-5))-induced mutation rate. Pretreatment of bacteria with Na2SeO3 alone had no effect on the spontaneous mutation level. The combined treatment of CHO cells with MNNG (1.25 x 10(-5) M) or tobacco smoke (TS, 2-3 puffs generated by a cigarette inhalation machine) plus Na2SeO3 (0.58-1.16 x 10(-5) M) starting 2 h and 4 h before the MNNG or TS treatment respectively resulted in a 2-3-fold increase in the percent of metaphases with chromosome aberrations. Furthermore, treatment for 7-14 days of male BDF1 (C57Bl x DBA2) or CC57W mice with Na2SeO3, added to the drinking water at a concentration of 10 ppm, potentiated by 2-3 times the chromosome-damaging activity of urethane (0.5-1.0 g/kg, i.p.) in mouse bone marrow, as measured by the formation of micronuclei or chromosome aberrations. In addition, Na2SeO3 increased up to 43.8% the number of micronucleated polychromatic erythrocytes (MNPCE) induced by mitomycin C (MMC, 1.5 mg/kg, i.p.) in BDF1 mouse bone marrow. Treatment of mice with Na2SeO3 alone had no effect on the spontaneous level of MNPCE. All these findings are consistent with a comutagenic and coclastogenic activity of selenium both in prokaryotes and in eukaryotes, in vitro as well as in vivo after pretreatment of target cells with the trace element.
authors.affiliation: Laboratory of Chemical Mutagenesis and Carcinogenesis, National Centre of Oncology, Sofia, Bulgaria.
authors.forename: R M
authors.initials: RM
authors.lastname: Balansky
mesh_terms: D000818:Animals; D002460:Cell Line; D002869:Chromosome Aberrations; D004912:Erythrocytes / Q000187:drug effects; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015162:Micronucleus Tests; D008861:Microsomes / Q000378:metabolism; D016685:Mitomycin; D008937:Mitomycins / Q000633:toxicity; D016296:Mutagenesis; D009153:Mutagens; D012486:Salmonella typhimurium; D012643:Selenium / Q000633:toxicity*; D014520:Urethane / Q000633:toxicity
chemical_list: D008937:Mitomycins; D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D014520:Urethane; D016685:Mitomycin; D008770:Methylnitrosourea; D012643:Selenium