Effect of modification by N-acetoxy-N-2-acetylaminofluorene on the level of DNA methylation

Abstract

DNA METHYLATION in prokaryotes as well as in eukaryotes is a widely distributed phenomenon but its biological role is still unknown. In prokaryotes, DNA methylation has been related to restriction recognition mechanisms1,2; no such correlation has yet been found in eukaryotes. Some investigators have suggested that cell differentiation and embryogenesis might be related to DNA methylation3–5. The recent results obtained by Christman et al.6 indicating that inhibition of DNA methylation may promote the differentiation and expression of globin genes in Friend erythroleukaemia cells, support this theory. In their observations, inhibition of DNA methylation was obtained after treatment of the cells with the methionine analogue L-ethionine which is also a carcinogen. We have used another approach where the change of levels of in vitro 5-methyl-3H-cytosine formation in DNA following DNA modification with a carcinogen is observed. We have chosen N-acetoxy-N-2-acetylaminofluorene (N- AcO-AAF) which reacts covalently in vitro and in vivo with nucleic acids and proteins7–9 and which, after administration to animals, induces tumours10.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Arber, W. & Linn, S. A. Rev. Biochem. 38, 467–500 (1969).

  2. 2

    Arber, W. Prog. Nucleic Acids Res. 14, 1–37 (1974).

  3. 3

    Scarano, E. Comp. Biochem. 28, 55–111 (1967).

  4. 4

    Holliday, R. & Pugh, J. E. Science 187, 226–232 (1975).

  5. 5

    Vanyushin, B. F., Mazin, A. L., Vasilyev, V. K. & Belozersky, A. N. Biochim. biophys. Acta 299, 397–403 (1973).

  6. 6

    Christman, J. K., Price, P., Pedrinan, L. & Acs, G. Eur. J. Biochem. 81, 53–61 (1977).

  7. 7

    Miller, E. C., Miller, J. A. & Hartmann, H. A. Cancer Res. 21, 815–824 (1961).

  8. 8

    Kriek, E. Biochim. biophys. Acta 161, 273–275 (1968).

  9. 9

    Agarwal, M. K. & Weinstein, I. B. Biochemistry 9, 503–507 (1970).

  10. 10

    Kriek, E. Biochim. biophys. Acta 355, 177–203 (1974).

  11. 11

    Salas, C. E. & Sellinger, O. Z. J. Neurochem. 31, 85–91 (1978).

  12. 12

    Miller, E. C., Juhl, U. & Miller, J. A. Science 153, 1125–1127 (1966).

  13. 13

    Fuchs, R. & Daune, M. Biochemistry, 11, 2659–2666 (1972).

  14. 14

    Fuchs, R. & Daune, M. FEBS Lett. 14, 206–208 (1971).

  15. 15

    Fuchs, R. & Daune, M. FEBS Lett. 34, 295–298 (1973).

  16. 16

    Fuchs, R. P. P. Nature 257, 151–152 (1975).

  17. 17

    Fuchs, R. P. P., Lefèvre, J. F., Pouyet, J. & Daune, M. P. Biochemistry 15, 3347–3351 (1976).

  18. 18

    Lefèvre, J. F., Fuchs, R. P. P. & Daune, M. P. Biochemistry 17, 2561–2567 (1978).

  19. 19

    Levine, A. F., Fink, L. M., Weinstein, I. B. & Grunberger, D. Cancer Res. 34, 319–327 (1974).

  20. 20

    Millette, R. L. & Fink, L. M. Biochemistry 14, 1426–1432 (1975).

  21. 21

    Berthold, V., Thielmann, H. W. & Geider, K. FEBS Lett. 86, 81–84 (1978).

  22. 22

    Drahovsky, D. & Morris, N. R. J. molec. Biol. 57, 475–484 (1971).

  23. 23

    Drahovsky, D. & Morris, N. R. J. molec. Biol. 61, 343–356 (1971).

  24. 24

    Drahovsky, D. & Morris, N. R. Biochim. biophys. Acta 277, 245–250 (1972).

  25. 25

    Kalousek, F. & Morris, N. R. J. biol. Chem. 244, 1151–1163 (1969).

  26. 26

    Pogo, A. O., Allfrey, V. G. & Mirsky, A. Proc. natn. Acad. sci. U.S.A. 56, 550–557 (1966).

  27. 27

    Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. J. molec. Biol. 193, 265–275 (1951).

  28. 28

    Kay, F. R. M., Simmons, N. S. & Dounce, A. L. J. Am. chem. Soc. 74, 1724–1726 (1952).

  29. 29

    Lotlikar, P. D., Scribner, J. D., Miller, J. A. & Miller, E. C. Life sci. 5, 1263–1269 (1969).

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

SALAS, C., PFOHL-LESZKOWICZ, A., DIRHEIMER, G. et al. Effect of modification by N-acetoxy-N-2-acetylaminofluorene on the level of DNA methylation. Nature 278, 71–72 (1979). https://doi.org/10.1038/278071a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.