Comet assay studies indicate that caffeine-mediated increase in radiation risk of embryos is due to inhibition of DNA repair.

It is well known that under specific conditions caffeine is able to enhance radiation risk of mammalian cells by a factor of approximately 1.5-2. Various mechanisms are discussed in the literature as possible explanations for this interaction. Inhibition of DNA repair plays a crucial role in the discussion, although direct evidence for this assumption is difficult to obtain. We used the "comet assay' in order to analyse the significance of repair inhibition by caffeine in the two-cell stage of mammalian gestation. Our data show that at the concentration necessary for increasing radiation risk (2 mM), caffeine effectively inhibits the restitution of radiation-damaged DNA.

[1]  P. Olive,et al.  The comet assay: a comprehensive review. , 1995, Mutation research.

[2]  A. Spindle,et al.  Induction of sister chromatid exchange in preimplantation mouse embryos in vitro by 3H-thymidine or ultraviolet light in combination with caffeine. , 1986, Teratogenesis, carcinogenesis, and mutagenesis.

[3]  A. Lehmann Effect of caffeine on DNA synthesis in mammalian cells. , 1972, Biophysical journal.

[4]  W Böcker,et al.  Comet assay studies of radiation-induced DNA damage and repair in various tumour cell lines. , 1994, International journal of radiation biology.

[5]  C. Streffer,et al.  Effects of a combination of X-rays and caffeine on preimplantation mouse embryos in vitro , 1983, Radiation and environmental biophysics.

[6]  R. Rowley,et al.  Modification of radiation-induced division delay by caffeine analogues and dibutyryl cyclic AMP. , 1982, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[7]  W. Müller Toxicity of various combinations of X-rays, caffeine, and mercury in mouse embryos. , 1989, International journal of radiation biology.

[8]  B. Kimler,et al.  The effect of caffeine on radiation-induced division delay. , 1977, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[9]  H. Lang Model for repair inhibition by caffeine , 1975 .

[10]  B. Hogan,et al.  Carbohydrate changes in pre- and peri-implantation mouse embryos as detected by a monoclonal antibody. , 1983, Cell differentiation.

[11]  R. Wegner,et al.  Caffeine-mediated release of alpha-radiation-induced G2 arrest increases the yield of chromosome aberrations. , 1983, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[12]  L. R. Gurley,et al.  Effects of caffeine on radiation-induced phenomena associated with cell-cycle traverse of mammalian cells. , 1974, Biophysical journal.

[13]  K J Johanson,et al.  Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. , 1984, Biochemical and biophysical research communications.

[14]  A. Sancar,et al.  Molecular mechanisms of DNA repair inhibition by caffeine. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[15]  C. Lücke‐Huhle Alpha-irradiation-induced G2 delay: a period of cell recovery. , 1982, Radiation research.

[16]  C. Streffer,et al.  Radiation Risk from Combined Exposures to Ionizing Radiations and Chemicals , 1984 .

[17]  C. Streffer,et al.  Relation between rate of cell proliferation and formation of micronuclei after combined treatment with X-rays and caffeine , 1993, Radiation and environmental biophysics.

[18]  J. Scaife Cyclic 3'-5'-adenosine monophosphate: its possible role in mammalian cell mitosis and radiation-induced mitotic G2-delay. , 1971, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[19]  R. Painter,et al.  Effect of caffeine on DNA synthesis in irradiated and unirradiated mammalian cells. , 1980, Journal of molecular biology.

[20]  B. Kihlman,et al.  The enhancement by caffeine of the frequencies of chromosomal aberrations induced in plant and animal cells by chemical and physical agents. , 1974, Mutation research.

[21]  B. Kihlman Caffeine and chromosomes , 1977 .

[22]  A. Boynton,et al.  Effects of caffeine on radiation-induced mitotic inhibition in S-180 ascites tumor cells. , 1974, Radiation research.

[23]  R. W. Jones,et al.  The action of caffeine on X-irradiated HeLa cells. I. Delayed inhibition of DNA synthesis. , 1977, Radiation research.

[24]  M. Green,et al.  The single cell gel electrophoresis assay (comet assay): a European review. , 1993, Mutation research.

[25]  C. Streffer,et al.  Supraadditive formation of micronuclei in preimplantation mouse embryos in vitro after combined treatment with X-rays and caffeine. , 1985, Teratogenesis, carcinogenesis, and mutagenesis.

[26]  W. Dewey,et al.  Comparative studies of the effects of drugs on X-ray-induced G2 delay. , 1978, Radiation research.

[27]  R. W. Jones,et al.  The action of caffeine on X-irradiated HeLa cells. III. Enhancement of X-ray-induced killing during G2 arrest. , 1978, Radiation research.

[28]  C. Streffer,et al.  Association of protein phosphorylation and cell cycle progression after X-irradiation of two-cell mouse embryos. , 1991, International journal of radiation biology.