Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Dec;71(12):4955–4959. doi: 10.1073/pnas.71.12.4955

Unscheduled DNA Synthesis in the Germ Cells of Male Mice Exposed In Vivo to the Chemical Mutagen Ethyl Methanesulfonate

Gary A Sega 1
PMCID: PMC434018  PMID: 4373737

Abstract

An unscheduled DNA synthesis has been clearly demonstrated in meiotic and postmeiotic germ cell stages of the male mouse after in vivo treatment with a 250 mg/kg dose of ethyl methanesulfonate. The germ cell stages showing unscheduled DNA synthesis range from early to middle meiotic prophase stages through early to middle spermatid stages. The initiation of this synthesis, taken to be repair of chemically damaged DNA in these germ cells, is rapid, beginning within 1 hour after the injection of ethyl methanesulfonate. Unscheduled DNA synthesis has not been detected in the most mature germ cell stages, which give rise to dominant lethal mutations, nor does it occur in germ cell stages where protamine has replaced the chromosomal histones.

Keywords: spermatogenesis, sperm protamine, dominant lethal mutations

Full text

PDF
4955

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brookes P., Lawley P. D. The reaction of mono- and di-functional alkylating agents with nucleic acids. Biochem J. 1961 Sep;80(3):496–503. doi: 10.1042/bj0800496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cattanach B. M., Pollard C. E., Isaacson J. H. Ethyl methanesulfonate-induced chromosome breakage in the mouse. Mutat Res. 1968 Sep-Oct;6(2):297–307. doi: 10.1016/0027-5107(68)90045-6. [DOI] [PubMed] [Google Scholar]
  3. Chang L. O., Looney W. B. A biochemical and autoradiographic study of the in vivo utilization of tritiated thymidine in regenerating rat liver. Cancer Res. 1965 Nov;25(10):1817–1822. [PubMed] [Google Scholar]
  4. Cumming R. B., Walton M. F. Fate and metabolism of some mutagenic alkylating agents in the mouse. I. Ethyl methanesulfonate and methyl methanesulfonate at sublethal dose in hybrid males. Mutat Res. 1970 Oct;10(4):365–377. doi: 10.1016/0027-5107(70)90049-7. [DOI] [PubMed] [Google Scholar]
  5. Ehling U. H., Cumming R. B., Malling H. V. Induction of dominant lethal mutations by alkylating agents in male mice. Mutat Res. 1968 May-Jun;5(3):417–428. doi: 10.1016/0027-5107(68)90011-0. [DOI] [PubMed] [Google Scholar]
  6. Generoso W. M., Russell W. L., Huff S. W., Stout S. K., Gosslee D. G. Effects of dose on the induction of dominant-lethal mutations and heritable translocations with ethyl methanesulfonate in male mice. Genetics. 1974 Aug;77(4):741–752. doi: 10.1093/genetics/77.4.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Generoso W. M., Russell W. L. Strain and sex variations in the sensitivity of mice to dominant-lethal induction with ethyl methanesulfonate. Mutat Res. 1969 Nov-Dec;8(3):589–598. doi: 10.1016/0027-5107(69)90077-3. [DOI] [PubMed] [Google Scholar]
  8. LAWLEY P. D., BROOKES P. FURTHER STUDIES ON THE ALKYLATION OF NUCLEIC ACIDS AND THEIR CONSTITUENT NUCLEOTIDES. Biochem J. 1963 Oct;89:127–138. doi: 10.1042/bj0890127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lam D. M., Bruce W. R. The biosynthesis of protamine during spermatogenesis of the mouse: extraction, partial characterization, and site of synthesis. J Cell Physiol. 1971 Aug;78(1):13–24. doi: 10.1002/jcp.1040780104. [DOI] [PubMed] [Google Scholar]
  10. Louie A. J., Dixon G. H. Kinetics of enzymatic modification of the protamines and a proposal for their binding to chromatin. J Biol Chem. 1972 Dec 25;247(24):7962–7968. [PubMed] [Google Scholar]
  11. Loveless A. Possible relevance of O-6 alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosamides. Nature. 1969 Jul 12;223(5202):206–207. doi: 10.1038/223206a0. [DOI] [PubMed] [Google Scholar]
  12. MONESI V. Autoradiographic study of DNA synthesis and the cell cycle in spermatogonia and spermatocytes of mouse testis using tritiated thymidine. J Cell Biol. 1962 Jul;14:1–18. doi: 10.1083/jcb.14.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Michel T. M., Legator M. S. DNA repair synthesis and chromosomal aberrations induced in vivo by triethylenemelamine. Mutat Res. 1974 Jul;24(1):41–45. doi: 10.1016/0027-5107(74)90045-1. [DOI] [PubMed] [Google Scholar]
  14. Monesi V. Synthetic activities during spermatogenesis in the mouse RNA and protein. Exp Cell Res. 1965 Aug;39(1):197–224. doi: 10.1016/0014-4827(65)90023-6. [DOI] [PubMed] [Google Scholar]
  15. OAKBERG E. F. A description of spermiogenesis in the mouse and its use in analysis of the cycle of the seminiferous epithelium and germ cell renewal. Am J Anat. 1956 Nov;99(3):391–413. doi: 10.1002/aja.1000990303. [DOI] [PubMed] [Google Scholar]
  16. OAKBERG E. F. Duration of spermatogenesis in the mouse and timing of stages of the cycle of the seminiferous epithelium. Am J Anat. 1956 Nov;99(3):507–516. doi: 10.1002/aja.1000990307. [DOI] [PubMed] [Google Scholar]
  17. RUSSELL W. L. X-ray-induced mutations in mice. Cold Spring Harb Symp Quant Biol. 1951;16:327–336. doi: 10.1101/sqb.1951.016.01.024. [DOI] [PubMed] [Google Scholar]
  18. Roberts J. J., Crathorn A. R., Brent T. P. Repair of alkylated DNA in mammalian cells. Nature. 1968 Jun 8;218(5145):970–972. doi: 10.1038/218970a0. [DOI] [PubMed] [Google Scholar]
  19. Roberts J. J., Pascoe J. M., Smith B. A., Crathorn A. R. Quantitative aspects of the repair of alkylated DNA in cultured mammalian cells. II. Non-semiconservative DNA synthesis ('repair synthesis') in HeLa and Chinese hamster cells following treatment with alkylating agents. Chem Biol Interact. 1971 Feb;3(1):49–68. doi: 10.1016/0009-2797(71)90025-1. [DOI] [PubMed] [Google Scholar]
  20. Sega G. A., Cumming R. B., Walton M. F. Dosimetry studies on the ethylation of mouse sperm DNA after in vivo exposure to (3H)ethyl metanesulfonate. Mutat Res. 1974 Sep;24(3):317–333. doi: 10.1016/0027-5107(74)90179-1. [DOI] [PubMed] [Google Scholar]
  21. Wagner R. P. Genetics and phenogenetics of mitochondria. Science. 1969 Mar 7;163(3871):1026–1031. doi: 10.1126/science.163.3871.1026. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES