DNA response to bleomycin in mammalian cells with variable degrees of chromatin condensation.
BLM induces DNA degradation in living cells. We used CHO cells with maximal chromatin compactness (cells synchronized in metaphase), cells with chromatin decondensed by Na butyrate treatments, and control cells with normal chromatin condensation in order to analyse the correlation between chromatin compactness, DNA sensitivity to BLM, efficiency of repair of BLM-induced DNA lesions, and cell viability. We found that the DNA sensitivity to BLM and the efficiency of DNA repair is inversely correlated with the degree of chromatin coiling. Cells with decondensed chromatin are those showing higher DNA sensitivity to BLM but also those having the best efficiency to mend the damage. Accordingly, these cells show an amount of residual DNA lesions and a curve of growth similar to that of control cells. The situation is just the opposite for metaphase cells. The DNA of these cells is more resistant to BLM, but the damage is poorly repaired. The final result is that BLM induces a higher concentration of residual DNA lesions and a lower viability in metaphase than in control cells. Our results suggest that chromatin structure influences the quantity and reparability of the BLM-induced lesions, producing a higher incidence of double strand break in the DNA of cells with marked chromatin condensation.
Lopez-Larraza
D M
DM
IMBICE, La Plata, Argentina.
Bianchi
N O
NO
D000704:Analysis of Variance; D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004260:DNA Repair; D006657:Histones / Q000737:chemistry; D008677:Metaphase; D009153:Mutagens / Q000633:toxicity*; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D013997:Time Factors
D002843:Chromatin; D006657:Histones; D009153:Mutagens; D001761:Bleomycin