Dose-rate-effects in XRCC1 wild-type and mutant CHO cell lines using An ²⁴¹AM source

Abstract

This work explores the effects of low-dose-rate radiation on both the AA8 (wild-type CHO cells) and EM9 (XRCC1 null CHO mutants) cell lines. In particular, this study performed clonogenic survival and growth assays to determine the radiations/ effect on the cells proliferative capacity. It was hypothesized that the XRCC1 null mutants would show greater radiosensitivity during continuous low-dose-rate radiation since the inability to rapidly respond to DNA damage would result in the gradual accumulation of cytotoxic double strand DNA breaks and/or chromosome exchanges/aberrations. The cells were irradiated for 7 days with photons from unencapsulated 241Am plate sources for chronic, low-dose-rate studies, at dose-rates between 1.99 ± .610 x 10-3 cGy/h and 1.23 ± .0325 cGy/h, and irradiated with a Phillips RT250 X-ray machine at 250 kVp and 2.5 Gy/min to doses between 0.02-10 Gy for acute studies. There were significant differences in the growth rates of the unirradiated controls and the irradiated flasks at all dose-rates for both AA8s and EM9s (except for the EM9 9.08 ± .390 x 10-3 cGy/h flask where p<.10). There were also suggestive (p<.20) differences in the clonogenic survival for both cell lines compared to controls with significant (p<.05) differences observed in the EM9 irradiated population at dose-rates of: 6.89 ± .315 x 10-3 cGy/h, 3.30 + .80 x 10-3 cGy/h, and 1.99 + .61 x 10-3 cGy/h. Moreover, there are suggestive (p<.15) trends indicating that XRCC1 deficient cells are more susceptible to chronic low-dose-rate radiation (dose-rates compared were between 1.99 ± .61 x 10-3 cGy/hand 9.08 + .39 x 10-3 cGy/h) as compared with acute exposures at the same dose.

(cont.) Despite some procedural differences with other published works, these results may be evidence of the "inverse dose-rate" effect noted by other authors.