Transplacental genotoxicity of triethylenemelamine, benzene, and vinblastine in mice.
Transplacental cytogenetic effects of triethylenemelamine (TEM), benzene, and vinblastine on maternal mice and their fetuses have been investigated using micronucleus and sister chromatid exchange (SCE) as genetic endpoints. CD-1 mice were treated on day 14 and 15 of gestation with TEM (0.125, 0.25, and 0.5 mg/kg), benzene (439,878, and 1,318 mg/kg), and vinblastine (0.5, 1, and 2 mg/kg) by intraperitoneal injection at 24 hr intervals, and sacrificed 40 hr after the first injection. Erythrocytic precursor cells in maternal bone marrow and fetal livers (2-4) from each pregnant mouse were used for the micronucleus and/or the SCE analyses. Significant dose-related increases in both micronuclei and SCE were found in maternal bone marrow and fetal liver following TEM treatment. Benzene at the highest dose (1,318 mg/kg) also caused a significant increase in micronuclei and SCE in both maternal bone marrow and fetal liver cells. The embryonic genotoxic effect of TEM was much higher than that of benzene for both genetic endpoints, and the frequency of micronuclei induced by benzene was higher in fetal liver than in maternal bone marrow cells. Vinblastine, a spindle poison, induced micronuclei but not SCE. Micronuclei induction by vinblastine was 7 fold greater in maternal bone marrow than in fetal liver cells. All three chemicals were cytotoxic in maternal bone marrow cells, but not in fetal liver cells except for TEM, which showed a weak cytotoxicity in fetal liver cells in the micronucleus assay. These results indicate that TEM, benzene, and vinblastine are transplacental genotoxicants in mice.
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505.
S G
SG
Xing
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Shi
Z L
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Wu
J K
JK
Chen
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Wallace
W Z
WZ
Whong
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T
Ong
D000818:Animals; D001554:Benzene / Q000008:administration & dosage / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D005260:Female; D007274:Injections, Intraperitoneal; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008431:Maternal-Fetal Exchange; D051379:Mice; D008815:Mice, Inbred Strains; D015162:Micronucleus Tests; D009153:Mutagens / Q000008:administration & dosage*; D011247:Pregnancy; D012854:Sister Chromatid Exchange; D014265:Triethylenemelamine / Q000008:administration & dosage / Q000633:toxicity*; D014747:Vinblastine / Q000008:administration & dosage / Q000633:toxicity*
D009153:Mutagens; D014747:Vinblastine; D014265:Triethylenemelamine; D001554:Benzene