Cross-sensitivity to DNA-damaging agents in radiation-sensitive mutants of murine leukemia cells

Two independently isolated radiation-sensitive mutants, M10 and LX830, of mouse L5178Y cells were compared for their sensitivity to various DNA-damaging agents. These two mutants share hypersensitivity to gamma rays, bleomycin, arabinofuranosyl cytosine (Ara-C) and aphidicolin. But they differ in that M10 is more sensitive to killing by methyl methanesulfonate (MMS) than LX830 or L5178Y, whereas LX830 is more sensitive to inactivation by hydroxyurea and 3-aminobenzamide than M10 or L5178Y. The response to mitomycin C (MMC) and 4-nitroquinoline-1-oxide (4NQO) is the most pronounced in M10, the least in L5178Y and intermediate in LX830. The complementation tests between M10 and LX830 showed that the X-ray survival curves of M10-LX830 hybrid cells were similar to those of M10 or LX830. An MMS-resistant clone was found among MMS-sensitive M10 cells and proved to be just as sensitive to killing by X-rays as the original M10 cells. These results indicate that M10 and LX830 have a common defect in the repair of damage caused by X rays, bleomycin, Ara-C and aphidicolin but a different defect in the repair of MMS-, MMC-, 4NQO-, hydroxyurea- and 3-aminobenzamide-damage. (author)