Transplacental genotoxicity of triethylenemelamine, benzene, and vinblastine in mice.
Xing-SG; Shi-X; Wu-L; Chen-K; Wallace-W; Whong-Z; Ong-T
Teratog, Carcinog, Mutagen 1992 Jan; 12(5):223-230
The genotoxicity of triethylenemelamine (51183) (TEM), benzene (71432), and vinblastine (865214) was investigated in transplacentally exposed mice. Groups of four female CD-1-mice were administered each test chemical by intraperitoneal injection on gestation day 14, and a second injection was given 24 hours (hr) later. Dose rates were 0.125, 0.25, and 0.5mg/kg of TEM, 439, 878, and 1318mg/kg of benzene, and 0.5, 1.0, and 2.0mg/kg of vinblastine. Animals were sacrificed at 40hr (for TEM and benzene), or 30hr (for vinblastine) after the first injection, and maternal bone marrow and fetal liver were sampled randomly for sister chromatid exchanges (SCE) and micronuclei (MN) formation as genetic endpoints. Results showed that TEM caused significant increases in MN and SCE of both erythrocytic precursor cells of the maternal bone marrow and fetal liver cells. Benzene produced the same results only at the highest concentration used, although even at this concentration, genotoxicity was lower than that of TEM. Benzene induced MN frequency was higher in fetal liver than in the maternal bone marrow. Vinblastine toxicity resulted in MN induction at a level seven times higher in maternal bone marrow than in fetal liver. SCE were absent with vinblastine treatment. The authors conclude that all three chemicals act as transplacental genotoxins and cause cytogenetic changes in bone marrow cells, with TEM being the most potent and benzene the weakest among them, and that maternal sensitivities are different to fetal sensitivities to these compounds.
NIOSH-Author; Blood-cells; Carcinogens; Chromosome-damage; Comparative-toxicology; Cytotoxic-effects; DNA-damage; Fetus; Genetic-factors; Hepatotoxicity; Laboratory-animals; Mutagens; Teratogens; Transplacental-exposure;
Author Keywords: SCE; micronucleus; benzene; triethylenemelamine; vinblastine
W.-Z. Whong, Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV 26505
51-18-3; 71-43-2; 865-21-4
Teratogenesis, Carcinogenesis, and Mutagenesis