Induction of micronuclei in bone marrow by triethylenemelamine (51183) (TEM), mitomycin-C (50077) (MMC), dimethylbenzanthracene (57976) (DMBA), and vincristine (57227) was studied in rats. Male Sprague-Dawley-rats were injected intraperitoneally with 0.25, 0.50, or 1.0mg/kg TEM, 0.05, 0.1, or 0.2mg/kg vincristine, 1, 2, or 4mg/kg MMC, or 50, 100, or 150mg/kg DMBA. They were killed 6, 12, 24, 48, or 72 hours later and the femoral bone marrow was obtained. Bone marrow polychromatic erythrocytes (PCEs) were isolated and scored for micronuclei. The PCE/normochromatic erythrocyte (PCE/NCE) ratios were determined. TEM increased the frequency of micronucleated PCEs; however, a clear dose response was seen only at 48 hours. The 1mg/kg dose caused a significant decrease in the PCE/NCE ratio indicating significant toxicity to the bone marrow erythropoietic system. Vincristine caused a dose dependent increase in PCE micronuclei frequency at the 6, 12, 24, and 48 hour sampling points. The 0.1 and 0.2mg/kg doses decreased PCE/NCE ratios at 24 and 48 hours. MMC significantly increased the micronucleated PCE frequency at 24, 48, and 72 hours. The peak responses occurred at 24 and 48 hours. The 2 and 4mg/kg doses significantly decreased the PCE/NCE ratio. DMBA at 50mg/kg caused a significant increase in PCE micronuclei frequency only at 24 hours. The 100 and 150mg/kg doses increased the micronuclei frequency at 24, 48, and 72 hours. DMBA decreased the PCE/NCE ratio at 48 and 72 hours. The magnitude of the responses induced by DMBA was lower than those induced by TEM, vincristine, and MMC. The authors conclude that TEM, vincristine, MMC, and DMBA induce micronuclei in rat bone marrow. The magnitude of the responses depends on dose and sampling time. Sampling times of 24 and 48 hours appear to be the most appropriate.
Tong-Man Ong, NIOSH, Microbiology Section, 944 Chestnut Ridge Road, Morgantown, WV 26505-2888