|Budget Amount *help
¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1993 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1992 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Acute chromosome-damaging and chromatid-rearranging capacities of various mutagens and carcinogenes such as 7,12-dimethylbenz(a)anthracene(DMBA), and N-nitroso-N-methylurea(NMU) were studied with rat bone marrow cells, liver cells and fibroblasts in vivo and in vitro. The frequency of chromosome aberrations(CA) and sister chromatid exchange(SCE) after administration of above-mentioned carcinogens was tested under various stimuli. The incidence of DMBA-and NMU-induced CA in the anemic rats was 45% and 56%, and in the polycythemic rats, it was 17% and 24%(normal rats 28-33%). However, the incidence of CA in polycythemic rats inoculated with 6 Units of erythropietin at the time of DMBA injection was 41% and 47%. In the other words, the percentage of metaphase cells with CA induced by DMBA was enhanced by anemia andsuppressed by polycythemia. The low incidence of CA in polycythemic rats was re-versed by 6 units of sheep erythropoietin injected at the time of DMBA and NMU treatment. CA were distributed nonrandomly in chromosomes 1 and 2. One region, the 40% region from the centromere(1q31), of the long arm of chromosome 1, and three regions, 30, 55 and 80% from the centromere(2q21, 2q25, 2q41), of chromosome 2 were extremely susceptible to DMBA and NMU in the normal hematopietic state. Also, the enhancing effect of erythropoietin on DMBA- and NMU- induced CA was considered specific with respect to chromosomal regions. The frequency of SCE was increased under the condition of anemia and that of SCE was decreased under the condition of polycythemia. In liver cell obtained hepatectomized rats, the frequency of SCE induced by DMBA was enhanced with addition of the liver cell growth factor in vivo(from 13.5% to 28.3%). In fibroblasts, the frequency of SCE induced by NMU was enhanced in the ratio of 1.5 times with addition of thefibroblastic growth factor in cultured medium in vitro.