Enhancement of Induced Sister Chromatid Exchange and Chromosomal Aberrations by Inhibitors of DNA Repair Processes

Abstract

The effect of post-treatment with inhibitors of DNA synthesis (hydroxyurea, aphidicolin) and repair (caffeine, 3-aminobenzamide) on the frequencies of chromosomal aberrations and sister chromatid exchange (SCE) induced by mitomycin C and decarbamoyl mitomycin C both in Chinese hamster cells and in human lymphocytes in vitro has been studied. The data show that in the case of Chinese hamster and human lymphocytes mitomycin C-treated cells there is an increased frequency of both chromosomal aberrations and SCE after a G₂ post-treatment with the inhibitors, while no increase is observed for decarbamoyl mitomycin C-treated cells. Since SCE are DNA synthesis-dependent, phenomenon, an increase in the frequency of SCE also in the G₂ phase might suggest that after mitomycin C treatment there is a residual DNA synthesis still going on very late in the cell cycle.

References

1. Radmam M , Jeggo P . and Wagner R (1982). Chromosomal rearrangement and carcinogenesis. Mutat. Res. 98: 249–264.

2. Cairns J (1981). The origin of human cancers. Nature 289: 353–357.

3. Evans HJ and Scott D (1969). The induction of chromosome aberrations by nitrogen mustard and its dependence on DNA synthesis. Proc. J. Soc. Lond. (Biol) 173: 491–512.

4. Evans HJ (1977). Molecular mechanisms in the induction of chromosome aberrations. In: Progress in Genetic Toxicology, D Scott , BA Bridges , and FH Sobels (eds). Elsevier/North Holland, Amsterdam, pp. 57–74.

5. Kihlman BA (1977). Caffeine and Chromosome. Elsevier, Amsterdam.

6. Kihlman BA , Hansson K , Palitti F , Andersson HC , and Hartley-Asp B (1982). Potentiation of induced chromatid-type aberrations by hydroxyurea and caffeine in G2. In: “Progress in Mutation Research”, AT Natarajan , G Obe , and H Altman (eds). Elsevier, Amsterdam, Vol. 4, pp. 11–24.

7. Palitti F , Tanzarella C , Degrassi F , De Salvia R , Fiore M , and Natarajan AT (1983). Formation of chromatid-type aberrations in G2 stage of the cell cycle. Mutat. Res. 110: 343–350.

8. Wolff S , Bodycote S , and Painter RB (1974). Sister chromatid exchanges induced in Chinese hamster cells by U.V. irradiation of different stages of the cell cycle: The necessity for cells to pass through S. Mutat. Res. 25: 73–81.

9. Painter RB (1980). A replication model for sister chromatid exchange. Mutat. Res. 70: 337–341.

10.

10. Cleaver JE (1981). Correlations between sister chromatid exchange frequencies and replicon sizes. Exp. Cell. Res. 136: 27–30.

11.

11. Kihlman BA and Natarajan AT (1983). Potentiation of chromosomal aberrations by inhibitors of DNA repair. In: DMA Repair and Its Inhibition, A Collins , CS Downés , and RT Johnson (eds). IRL Press, Oxford (in press).

12.

12. Palitti F , Tanzarella C , Cozzi R , Ricordy R , and Fiore M (1982). Comparison of the frequencies of SCE induced by chemical mutagens in bone marrow, spleen, and spermatogonial cells of mice. Mutat. Res. 103: 191–195.

13.

13. Painter RB and Yong BR (1980). Radiosensitivity in Ataxia Talangiectasia, a new explanation. Proc. Natl. Acad. Sci. USA 77: 7315–7317.

14.

14. van't Hof J (1980). Pea (Pisum sativum) cells arrested in G2 have nascent DNA with breaks between replicons and replication clusters. Exp. Cell Res. 129: 231–237.