title: OH radicals from the indirect actions of X-rays induce cell lethality and mediate the majority of the oxygen enhancement effect.
abstract: We examined OH radical-mediated indirect actions from X irradiation on cell killing in wild-type Chinese hamster ovary cell lines (CHO and AA8) under oxic and hypoxic conditions, and compared the contribution of direct and indirect actions under both conditions. The contribution of indirect action on cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide, which suppresses indirect action by quenching OH radicals without affecting the direct action of X rays on cell killing. The contributions of indirect action on cell killing of CHO cells were 76% and 50% under oxic and hypoxic conditions, respectively, and those for AA8 cells were 85% and 47%, respectively. Therefore, the indirect action on cell killing was enhanced by oxygen during X irradiation in both cell lines tested. Oxygen enhancement ratios (OERs) at the 10% survival level (D10 or LD90) for CHO and AA8 cells were 2.68 ± 0.15 and 2.76 ± 0.08, respectively. OERs were evaluated separately for indirect and direct actions, which gave the values of 3.75 and 2.01 for CHO, and 4.11 and 1.32 for AA8 cells, respectively. Thus the generally accepted OER value of ∼3 is best understood as the average of the OER values for both indirect and direct actions. These results imply that both indirect and direct actions on cell killing require oxygen for the majority of lethal DNA damage, however, oxygen plays a larger role in indirect than for direct effects. Conversely, the lethal damage induced by the direct action of X rays are less affected by oxygen concentration.
authors.affiliation: a Next Generation Medical Physics Research Program.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Hirayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ito
authors.forename: Miho
authors.initials: M
authors.lastname: Noguchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Uzawa
authors.forename: Gen
authors.initials: G
authors.lastname: Kobashi
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Okayasu
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage / Q000528:radiation effects; D005260:Female; D017665:Hydroxyl Radical / Q000737:chemistry*; D010053:Ovary / Q000166:cytology / Q000528:radiation effects; D010100:Oxygen / Q000737:chemistry*; D014965:X-Rays
chemical_list: D017665:Hydroxyl Radical; D010100:Oxygen