小核試験感度増強に与えるCa2+拮抗剤の影響について

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In vitro and in vivo short term mutagenicity tests are widely used for screening environmental and industrial chemicals for carcinogenic potential. It is necessary to evaluate chemical carcinogens with the in vivo mutagenicity test system because of the difficulty of extrapolating the results of in vitro mutagenicity tests to human beings. But the in vivo mutagenicity test system has a low sensitivity for screening carcinogenic potential compared with the in vitro test.The in vivo micronucleus test developed by Schmid is commonly used because of its simplicity, reproducibility, and economic return. We have tried to modify this test to elevate its sensitivity.Verapamil is a calcium antagonist administered to patients with heart disease. It is known that verapamil has the ability to increase the permeability of the cell membrane. It is important that mutagens reach the DNA strands through the cell membrane in order to induce mutagenic changes of cells.The aim of this study is to investigate the effects of a calcium antagonist on the sensitivity of in vivo and in vitro micronucleus tests using vincristine as a mutagen.In the in vivo micronucleus test, both single and consecutive administration of verapamil showed a dose-response relationship between the dose of verapamil or vincristine and the incidence of micronucleated polychromatic erythrocytes (MPCE). However, there were no significant differences in MPCE incidence between single and consecutive administration of verapamil.On the other hand, in in vitro micronucleus test, the longer the incubation time of vincristine and verapamil with cultured bone marrow cells, the higher the MPCE induction rates. The dose-response relationship between the incidence of MPCE and the concentration of verapamil or vincristine was also observed in the in vitro micronucleus test.This present study suggests that the sensitivity of the micronucleus test can be increased by verapamil, a calcium antagonist.
日本衛生学会の論文

小核試験感度増強に与えるCa2+拮抗剤の影響について

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