Abstract
Recently, Copper(II)-diacetyl-bis(N4-methyothiosemicarbazone), Cu-ATSM, has been reported to concentrate in hypoxic tissues and cells. In this study, the chromosomal aberrations were investigated in Cu-ATSM treated cultured cells irradiated with monochromatic X rays at around K-shell absorption edge of the Cu atom. Exponentially growing human cells (GM05389, HSG) were incubated with 3000nM Cu-ATSM at both hypoxic and normoxic conditions for 10 hours. After Cu-ATSM treatment, cells were irradiated with monochromatic X rays having energy of 9.027 (CuK-H) and 8.973 keV (CuK-L) (corresponding energies to the slightly above and below the Cu K-shell absorption edge). Soon after the irradiation, the chromosomal aberrations were analyzed by premature chromosomal condensation (PCC) method using calyculin A. Under hypoxic conditions, cells took up Cu-ATSM significantly a lot compared with those treated under normoxic conditions, and the chromosomal aberrations induced by the irradiation with Cu-K edge X rays were much greater than those without Cu-ATSM. Also, chromosomal aberrations of Cu-ATSM treated cells irradiated with CuK-H X rays were greater than those irradiated with CuK-L X rays. This study shows clearly the enhancement of chromosomal aberrations of hypoxic cultured cells with Cu-ATSM by through ionization or excitation of Cu atoms in cells.
