ENHANCEMENT OF CHROMOSOME-ABERRATIONS BY THE COMBINATION OF DNA SUBSTITUTION WITH HALOGENATED DEOXYURIDINE AND STREPTONIGRIN TREATMENTS

We treated CHO cells with streptonigrin (SN) alone, in combination wit h BrdUrd or IdUrd substitution, and with or without the addition of ca ffeine. The cells assessed for chromosome damage by SN were in the G(2 ) period and the magnitude of the damage was expressed as monosubstitu ted chromatid breaks, bisubstituted chromatid breaks and boundary regi ons breaks (boundary regions indicate the point of exchange of mono- a nd bisubstituted chromatids). We found that the combination of BrdUrd or IdUrd substitution with SN treatments produced a remarkable increas e in the frequency of breaks over the frequencies observed with the ha logenated compound only. The effect was more evident with IdUrd than w ith BrdUrd, and more dramatic in bisubstituted than in monosubstituted chromatids. The frequency of boundary breaks in cells treated with Br dUrd plus SN was similar to the frequency of breaks in monosubstituted chromatids treated similarly. Conversely, the damage in boundary regi ons was almost similar to that in bisubstituted chromatids in cells ch allenged with IdUrd plus SN. The addition of caffeine to BrdUrd-substi tuted chromosomes gave rise to a marked enhancement of breakages with a gradient of chromatid damage that was: bisubstituted > monosubstitut ed > boundary regions. A further increase of chromatin breaks maintain ing the gradient indicated above was obtained when the cells were trea ted with BrdUrd plus SN plus caffeine. We propose that BrdUrd and IdUr d substitution alone or in combination with caffeine treatments and wi th SN in its capacity to bind DNA, give rise to different chromatin st ructures capable of modulating the DNA damage induced along the chroma tin fibril by the active oxygen species liberated by SN-DNA complexes.