Results of the Genotoxic Action of Antimony Ions with Attachments and Cover Letter Dated 06/15/1988

摘要

Antimony chloride (CAS No. 10025-91-9) was evaluated for genotoxicity in Swiss mice (5-14/group, sex ratio unspecified) administered doses of 0.5, 1.0 and 1.5 g/kg, by oral gavage as 50% solution in DMSO. Control mice were untreated. Mice were sacrificed at 24, 48, and 72 hours post-treatment for splenectomy with respective 3,000,000 cell/ml aliquot tissue samples (suspensions in phosphate-buffered saline) dispensed for determination of splenic antimony content (mg/g spleen tissue), and rates of treatment-related DNA damage and repair. Nucleoid sedimentation, and replicative DNA-synthesis and repair incorporation of 3H-thymidine into DNA after irradiation were evaluated. Upon neutron-activation analysis, levels of antimony chloride present in spleens of orally treated mice were found to reflect dose level. Analysis of irradiated cells disclosed an antimony-122 energy of 564 keV and a half-life of 2.7 days and antimony concentrations were found to diminish over the 3-day observation period at all treatment levels. Oral antimony chloride was associated with dose-related incidence of DNA-strand breaks. Additionally, nucleoid sedimentation illustrated more frequent fragmentation among early (24-hour) sacrifices due to declining levels of antimony in the 48- and 72-hour sacrifice groups. The degree of fragmentation was notably dose-related. Gamma-irradiation could not further enhance DNA damage to the small fragments remaining after treatment at 1.5 g/mg as it did in cells from control, low-dose and mid-dose mice. Further, the spontaneous repair of damage from gamma-irradiation noted among control, low-, and mid-dose groups was inhibited in cells from high-dose, 24-hour sacrificed mice to nearly imperceptible by nucleoid sedimentation analysis. Inhibited DNA repair following gamma-irradiation also reflected higher relative antimony levels in early (24-hour) sacrifices among the other dosage groups. Slowed incorporation of labelled thymidine confirmed slowed DNA repair in treated cells after UV254 irradiation as it indicated impaired DNA synthesis in non-irradiated cells. Again, inhibitory effects were greatest in association with the highest levels of antimony (high dose, early sacrifice mice). There was no detectable inhibition of 3H-thymidine incorporation in cells of 72-hour sacrifices.