DO DNA DOUBLE-STRAND BREAKS INDUCED BY ALU-I LEAD TO DEVELOPMENT OF NOVEL ABERRATIONS IN THE 2ND AND 3RD POSTTREATMENT MITOSES

Several authors have reported that ionizing radiation can give rise to novel aberrations several mitotic divisions after the exposure. At ou r institute this phenomenon has been observed in mouse preimplantation embryos. This cell system is uniquely well suited for such investigat ions because the first three cell divisions show a high degree of sync hrony. Thus the expression of chromosomal aberrations at the first, se cond and third mitosis after irradiation can be scored unambiguously. To investigate whether DNA double-strand breaks may be the lesions res ponsible for the delayed expression of chromosomal aberrations, we hav e studied the frequencies of aberrations in the first, second and thir d mitosis after treatment of one-cell mouse embryos with the restricti on enzyme Alu I. Embryos were permeabilized with Streptolysin-O. The r esults indicate that the induction of double-strand breaks does not le ad to novel aberrations in the third post-treatment mitosis. Several e mbryos scored at the second mitosis showed very high numbers of aberra tions, indicating that Alu I may remain active in the cells for a peri od of one cell cycle. After treatment with Streptolysin-O alone, enhan ced aberration frequencies were observed in the third post-treatment m itosis, suggesting that membrane damage has a delayed effect on the ce llular integrity. (C) 1996 by Radiation Research Society.