Effect of doxorubicin on cell survival and micronuclei formation in HeLa cells exposed to different doses of gamma-radiation.
OBJECTIVE
The present study was undertaken to obtain an insight into the combined effects of doxorubicin with radiation on the cell survival and micronuclei induction in HeLa cells.


METHODS
HeLa S3 cells were allowed to grow till they reached plateau phase, inoculated with 10 micrograms/ml doxorubicin hydrochloride and then exposed to 0, 0.5, 1, 2 and 3 Gy gamma-radiation. Clonogenicity of cells was measured using the colony forming assay, micronuclei formation using the micronucleus assay.


RESULTS
The treatment of HeLa cells with doxorubicin (adriamycin) for 2 hours before exposure to different doses of gamma-radiation resulted in a significant and dose-dependent decline in the cell survival and cell proliferation when compared to the PBS + irradiation group. Conversely, the frequency of micronuclei increased in a dose-related manner in both the PBS + irradiation and doxorubicin + irradiation groups. The pretreatment of HeLa cells with doxorubicin before irradiation to various doses of gamma-rays resulted in a significant elevation in the frequency of micronuclei when compared with the concurrent PBS + irradiation group. The dose-response relationship for both PBS + irradiation and doxorubicin + irradiation groups was linear. The correlation between cell survival and micronuclei induction was also determined for PBS or doxorubicin + irradiation group, where the clonogenicity of cells declined with the increase in micronuclei formation. The correlation between cell survival and micronuclei induction was linear quadratic for both PBS + irradiation and doxorubicin + irradiation groups.


CONCLUSIONS
From our study it can be concluded that combination treatment with doxorubicin and radiation increased the genotoxic effect of the either treatment given alone.
Jagetia
G C
GC
Department of Radiobiology, Kasturba Medical College, Manipal, India.
Nayak
V
V
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D004317:Doxorubicin / Q000494:pharmacology*; D005720:Gamma Rays; D006367:HeLa Cells / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D015162:Micronucleus Tests
D000970:Antineoplastic Agents; D004317:Doxorubicin