1987 Fiscal Year Final Research Report Summary
Mechanism of Chromosome aberrations induced by mutagen and carcinogen under the growth stimulation
| Project/Area Number |
61570176
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Ehime University |
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Principal Investigator |
UEDA Norifumi Ehime University, Associate Professor, 医学部, 助教授 (30030886)
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| Project Period (FY) |
1986 – 1987
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| Keywords | Growth factor / Chromosome aberrations / Sister chromatid exchanges / Mutagen and carcinogen / 発癌 |
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| Research Abstract |
Acute chromosome-damaging(CA) and chromatid-rearranging(SCE) capacities of various mutagens and carcinogenes such as 7,12-dimethylbenz(a)anthracene(DMBA), 7,8,12-trimethylbenz(a)anthracene(TMBA) and N-nitroso-N-methylurea were sutdied with rat bone marrow cells and fiblasts 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 CA in the anemic rats was 34% and in the polycythemic rats, it was 18%(normal rats 23%). However, the incidence of CA in polycythemic rats inoculated with 6 Units of erythropietin at the time of DMBA injection was 32%. Therefore, the percentage of metaphase cells with CA induced by DMBA was enhanced by anemia and suppressed by polycythemia. The low incidence of CA in polycythemic rats was reversed by 6 units of sheep erythropoietion injected at the time of DMBA treatment. CA were distributed nonrandomly in chromosomes 1 and 2. One region, the 40% region from the centromere, of the long arm of chromosome 1, and two regions, 30 and 55% from the centromere, of chromosome 2 were extremely susceptible to DMBA in the normal hematopoietic state. Also, the enhancing effect of erythropoietin on DMBA-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 fibroblasts, the frequency of SCE induced by NMU was enhanced with addition of fibroblastic growth factor in cultured medium in vitro.
In the TMBA-induced leukemogenesis, sex hormone may somehow be associated with carcinogenesis.
The above enhanced susceptibilityofcertainchromosomal regions to chemical carcinogens under growth stimuli is important in respect to the fact that growth stimuli given before carcinogen treatment enhance carcinogenesis in organs.
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