The induction of chromosome damage in CHO cells by beryllium and radiation given alone and in combination.
Studies were conducted to determine the effects of BeSO4 or X rays, alone and in combination, on cell cycle kinetics, cell killing, and the production of chromosome aberrations in Chinese hamster ovary (CHO) cells. The concentration of BeSO4 required to kill 50% of CHO cells exposed to BeSO4 for 20 h was determined to be 1.1 mM with 95% confidence intervals of 0.72 to 1.8 mM. During the last 2 h of the 20-h beryllium treatment (0.2 and 1.0 mM), cells were exposed to 0.0, 1.0, or 2.0 Gy of X rays. Exposure to either BeSO4 or X rays produced a change in cell cycle kinetics which resulted in an accumulation of cells in the G2/M stage of the cell cycle. However, combined exposure to both agents resulted in a block similar to that observed following exposure to X rays only. The background level of chromosome damage was 0.05 +/- 0.015 aberrations/cell in the CHO cells. Seven hours after the end of exposure to 0.2 and 1.0 mM beryllium, 0.03 +/- 0.003 and 0.09 +/- 0.02 aberrations/cell, respectively, were observed. The data for chromosome aberrations following X-ray exposure were fitted to a linear model with a coefficient of 0.14 +/- 0.01 aberrations/cell/Gy. When beryllium was combined with the X-ray exposure the interactive response was predicted by a multiplicative model and was significantly higher (P less than 0.05) than predicted by an additive model. The influence of time after radiation exposure on the interaction between beryllium and X rays was also determined. No interaction between beryllium and X-ray exposure in the induction of chromosome-type aberrations (P greater than 0.05) was detected. The frequency of chromatid-type exchanges and total aberrations was significantly higher (P less than 0.05) in the radiation plus beryllium-exposed cells when compared to cells exposed to X rays only, at both 9 and 12 h after X-ray exposure. These data suggest that the multiplicative interaction may be limited to cells in the S and G2 stages of the cell cycle.
Brooks
A L
AL
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Griffith
W C
WC
Johnson
N F
NF
Finch
G L
GL
Cuddihy
R G
RG
D000818:Animals; D001608:Beryllium / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002869:Chromosome Aberrations; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D066298:In Vitro Techniques; D011831:Radiation Genetics
C020711:beryllium sulfate; D004247:DNA; D001608:Beryllium