Micronucleus test of dibenz[ a, h]anthracene

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 weil as the micronucleus assay in mouse bone marrow. 4 h growth of S. typhimurium TA1535 in a nutrient broth containing 2.9 × 10−5 M but not 1.16 × 10−5 M Na2SeO3 caused an up to 10-fold increase of the number of Nmethylnitrosourea (MNU, 2.0–2.5 mM)-induced his+ revertants and an up to 2-fold elevation of N-methylN′-nitro-N-nitrosoguanidine (MNNG, 1.48 × 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 × 10−5 M) or tobacco smoke (TS, 2–3 puffs generated by a cigarette inhalation machine) plus Na2SeO3 (0.58–1.16 × 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 BDFI (C57B1 × 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.