Residual γH2AX foci as an indication of lethal DNA lesions

BMC Cancer

Table 1 Correlation between residual γH2AX and cell killing in SiHa monolayers exposed to DNA damaging agents

DNA damaging agent	Mechanism of interaction with DNA	Likely mechanism(s) of γH2AX formation	^aSlope (95% confidence limits) and correlation coefficient (r²)
X-rays	SSB, DSB, base damage	Direct DSBs	0.95 (0.57-1.33) r ² = 0.95
Etoposide	Topo II inhibitor	Direct DSBs	1.17 (0.91-1.44) r ² = 0.91
Temozolamide	Base alkylation	Base damage leading to DSBs during replication^b	0.62 (0.42-0.82) r ² = 0.82
MNNG	Base alkylation	Base damage leading to DSBs during replication^b	0.79 (0.52-1.07) r ² = 0.87
Cisplatin	Inter- and intra-strand crosslinks	Inter- and intra-strand crosslinks leading to DSBs during replication^b	0.77 (0.53-1.02) r ² = 0.87
Doxorubicin	SSB, DSB, base damage, topo II inhibitor	Direct DSBs and replication fork blockage leading to DSBs	0.95 (0.88-1.03) r ² = 0.99
Tirapazamine	SSB, DSB, base damage, topo II inhibitor	Direct DSBs and replication fork blockage leading to DSBs	1.06 (0.80-1.3) r ² = 0.90
Camptothecin	Topo I inhibitor	Replication fork blockage leading to DSBs	0.83 (0.61-1.04) r ² = 0.85
Hydrogen peroxide	SSB	Opposed single-strand breaks	1.06 (0.85-1.26) r ² = 0.93

^a The slope was obtained by plotting clonogenic surviving fraction versus the fraction of cells lacking foci.
^b After exposure to very high drug doses, γH2AX forms independently of cell cycle phase and may implicate opposed repair sites as responsible for triggering H2AX phosphorylation.

ISSN: 1471-2407