|Budget Amount *help
¥11,300,000 (Direct Cost : ¥11,300,000)
Fiscal Year 1994 : ¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1993 : ¥3,500,000 (Direct Cost : ¥3,500,000)
Fiscal Year 1992 : ¥5,700,000 (Direct Cost : ¥5,700,000)
The purpose of the present study is to develop a detection system for germ-cell mutagenesis with high sensitivity and multiple genetic endpoints using the Japanese Medaka Oryzias latipes. About ten years ago, we started developing a non-mammalian test system for detecting environmental germ-cell mutagenesis using the Japanese Medaka. In the middle of the FY 94, we succeeded in establishing a inbred tester strain with three marker loci (b/b ; gu/gu ; lf/lf) , named AA2 inbred strain, by repeating brother-sister mating for more that 20 filial generations. By February 8,1995, we have examined 872,961 embryos that correspond to 2,299,892 loci. Among these were the control with 195,554 embryos corresponding to 501,917 loci. The rate for spontaneous embryonic death was 5.6%, a value almost comparable to the reported one in the mouse (5.8%). The spontaneous total mutation rate and the spontaneous viable mutation rate were, respectively, 3.8x10-5/locus and 4.2x10-6/locus. In the present test system, we succeeded in integrating four genetic endpoints, i.e., dominant lethal mutation, total mutation, viable mutation and external malformation, into one individual, although the quantitation of external malformations was not as successful as the remaining three endpoints. These genetic endpoints showed good dose-response relationships for gamma-rays and fission neutron radiation. Furthermore, the extent of reduction of total mutation rate down to viable mutation rate was about 90%, irrespective of the difference in stages of maturation of male germ cells at the time of exposure to radiations.
However, exposure of male germ cells to ENU resulted in different reduction depending on the maturation stages as well as ENU concentration.