calicheamicin-gamma(1)i and Ataxia-Telangiectasia

The radiosensitive Chinese hamster V79 cell mutants (V-C4, V-E5 and V-G8), isolated previously in our laboratory, have been shown to resemble human ataxia telangiectasia (A-T) cells. These hamster cell mutants were further characterized with respect to cross-sensitivity to different radiomimetic agents and to mutation induction by X-rays. The data on cell survival (D10 values) show that they are hypersensitive to adriamycin (2-3-fold increase), etoposide (3-fold for V-G8 and 6-fold for V-E5 and V-C4), calicheamicin gamma 1I (4-fold) and streptonigrin (3-fold for V-G8 and V-C4, and 12-fold for V-E5). The frequency of X-ray-induced hprt mutations is slightly enhanced in the hamster mutant cells treated with the same dose. However, the mutants show similar mutability as parental V79 cells when considering the same survival level. The overall conclusion from these studies is that these hamster cell mutants mimic the phenotypic characteristics observed in cultured cells from A-T patients and, therefore, may be defective in the same repair pathway as their human counterparts.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Ataxia Telangiectasia; Cell Line; Cell Survival; Cricetinae; Doxorubicin; Enediynes; Etoposide; Humans; Hypoxanthine Phosphoribosyltransferase; Mutagens; Mutation; Streptonigrin

We report the hypersensitivity of SV40-transformed fibroblasts derived from ataxia telangiectasia (AT) patients to calicheamicin gamma 1I. In common with other free-radical generating agents such as bleomycin and ionizing radiation, treatment with calicheamicin gamma 1I reveals AT derived lines to be 6-fold more sensitive to this drug when compared to controls. Furthermore, in common with ionizing radiation, AT cells did not show dose-dependent inhibition of DNA synthesis after treatment with calicheamicin gamma 1I.

Topics: Aminoglycosides; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Ataxia Telangiectasia; Bleomycin; Cell Line; Cell Survival; Cell Transformation, Viral; DNA; Dose-Response Relationship, Drug; Enediynes; Fibroblasts; Mesylates