Carcinogen-induced chromosome breakage in chromosome instability syndromes

Abstract

Cultured fibroblasts from patients with chromosome instability syndromes (Fanconi's anemia (FA), ataxia telangiectasia (AT), Bloom's syndrome (BS), xeroderma pigmentosum (XP)) and from normal individuals were examined for their susceptibility to diepoxybutane (DEB)-induced chromosome breakage. Clear differences in patterns of spontaneous and induced chromosome breakage in the different syndromes were found. In two of the syndromes (FA and AT), chronic exposure to a low concentration of the carcinogen induced extensive chromosome damage without reduction in cell viability. Exposure to the same concentration of carcinogen had no clastogenic effect on BS, XP, or normal fibroblasts. Furthermore, when normal fibroblasts were exposed to a higher dose of the same chemical, there was significant reduction in viability with little increase in chromosome aberrations. These experiments separate the clastogenic effect of the carcinogen from its cytotoxic effect, and show genetic differences in susceptibility of cells to carcinogen-induced chromosome damage.