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DNA base sequence changes induced by diethyl sulfate in postmeiotic male germ cells of Drosophila melanogaster

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Summary

The DNA base sequence changes induced by diethyl sulfate (DES) were analyzed in postmeiotic male germ cells of Drosophila melanogaster. 31 transmissible vermilion mutants were recovered in F1 and F2 generations, with a frequency of 2.6 × 10−4 for the F1, and of 1.8−13 × 10−4 for the F2. The results show that DES induces both base pair substitutions (93%) and deletions (7%). In accord with its relatively high ability to alkylate oxygens in DNA, the most frequent type of sequence alteration among the basepair changes are GC-AT transitions, accounting for 73% of mutations, followed by transversions AT-TA (10%). DES also induced AT-GC transitions and AT-CG transversions. Both induced deletions were intralocus deletions, not occurring between basepair repeats. No influence of neighboring bases on the mutation position was found.

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References

  • Abrahamson S, Würgler FE, De Jongh C, Meyer HU (1980) How many loci on the X-chromosome of Drosophila melanogaster can mutate to recessive lethals? Environ Mutagen 2:447–453

    Google Scholar 

  • Ashman CR, Davidson RL (1987) DNA base sequence changes induced by ethyl methanesulfonate in a chromosomally integrated shuttle vector gene in mouse cells. Somat Cell Mol Genet 13:563–568

    Google Scholar 

  • Batzer MA, Tedeschi B, Fossett NG, Tucker A, Kilroy G, Arbour P, Lee WR (1988) Spectra of molecular changes induced in DNA of Drosophila spermatozoa by 1-ethyl-1-nitrosourea and X-rays. Mutat Res 199:255–268

    Google Scholar 

  • Beranek D (1990) Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents. Mutat Res 231:11–30

    Google Scholar 

  • Bignami M, Vitelli A, DiMuccio A, Terlizzese M, Calcagnile A, Zapponi GA, Lohman PHM, Den Engelse L, Dogliotti E (1988) Relationship between specific alkylated bases and mutation at two gene loci induced by ethylnitrosourea and diethyl sulfate in CHO cells. Mutat Res 193:43–51

    Google Scholar 

  • Burns PA, Allen FL, Glickman BW (1986) DNA sequence analysis of mutagenicity and site specificity of ethyl methanesulphonate in Uvr+ and UvrB− strains of Escherichia coli. Genetics 113:811–819

    Google Scholar 

  • Duran HL, Wani AA (1987) Site-specific gap-misrepair mutagenesis by O4-ethylthymine. Biochim Biophys Acta 908:60–69

    Google Scholar 

  • Eeken JCJ, Vreeken C, De Jong AWM, Pastink A (1991) The nature of X-ray-induced mutations after recovery in excision repair-deficient (mus-201) Drosophila females. Mutat Res 247:129–140

    Google Scholar 

  • Fortini P, Bignami M, Dogliotti E (1990) Evidence for AP site formation related to DNA-oxygen alkylation in CHO cells treated with ethylating agents. Mutat Res 236:129–137

    Google Scholar 

  • Fossett NG, Arbour-Reily P, Kilroy G, McDaniel M, Mahmoud J, Tucker AB, Chang SH, Lee WR (1990) Analysis of ENU-induced mutations at the Adh locus in Drosophila melanogaster. Mutat Res 231:73–85

    Google Scholar 

  • Glickman BW, Ripley LS (1984) Structural intermediates of deletion mutagenesis: A role for palindromic DNA. Proc Natl Acad Sci 81:512–516

    Google Scholar 

  • Hoffmann GR (1980) Genetic effects of dimethyl sulfate, diethyl sulfate, and related compounds. Mutat Res 75:63–129

    Google Scholar 

  • Ingle CA, Drinkwater NR (1989) Mutational specificites of 1′-acetoxysafrole, N-benzoyloxy-N-methyl-4-aminoazobenzene, and ethyl methanesulfonate in human cells. Mutat Res 220:133–142

    Google Scholar 

  • Kohler SW, Provost GS, Fieck A, Kretz PL, Bullock WO, Sorge JA, Putman DL, Short JM (1991) Spectra of spontaneous and mutagen-induced mutations in the lacI gene in transgenic mice. Proc Natl Acad Sci 88:7958–7962

    Google Scholar 

  • Lacy LR, Eisenberg MT, Osgood CJ (1986) Molecular analysis of chemically induced mutations at the RpII215 locus of Drosophila melanogaster. Mutat Res 162:47–54

    Google Scholar 

  • Lawley PD (1974) Some chemical aspects of dose-response relationships in alkylation mutagenesis. Mutat Res 23:283–295

    Google Scholar 

  • Lee CS, Curtis D, McCarron M, Love C, Gray M, Bender W, Chovnick A (1987) Mutations affecting expression of the rosy locus in Drosophila melanogaster. Genetics 116:55–66

    Google Scholar 

  • Lindsley DL, Grell EH (1968) Genetic variations of Drosophila melanogaster. Carnegie Inst Wash 627

  • Loeb LA, Preston BD (1986) Mutagenesis by apurinic/apirimidinic sites. Annu Rev Genet 20:201–230

    Google Scholar 

  • Muñoz ER, Mazar-Barnett B (1977) II–III translocations induced by diethyl sulfate in mature sperm of Drosophila melanogaster. Mutat Res 45:355–357

    Google Scholar 

  • Natarajan AT, Simons JWIM, Vogel EW, van Zeeland AA (1984) Relationship between killing, chromosomal aberrations, sister chromatid exchanges and point mutations induced by monofunctional alkylating agents in Chinese hamster cells. A correlation with different ethylation products in DNA. Mutat Res 128:31–40

    Google Scholar 

  • Nivard MJM (1991) Genetic and molecular analysis of alkylation-induced DNA damage in Drosophila melanogaster. Thesis. University of Leiden.

  • Nivard MJM, Patink A, Vogel EW (1992) Molecular analysis of mutations in the vermilion gene of Drosophila melanogaster by methyl methanesulfonate. Genetics, in press.

  • O'Brien SJ, MacIntyre RJ (1978) Genetics and biochemistry of enzymes and specific proteins of Drosophila. In: Wright TRF, Ashburner M (eds) The genetics and biology of Drosophila, vol 2a. Academic Press, New York, pp 396–551

    Google Scholar 

  • Pastink A, Vreeken C, Vogel EW (1988) The nature of N-ethyl-N-nitrosourea-induced mutations at the white locus of Drosophila melanogaster. Mutat Res 199:47–53

    Google Scholar 

  • Pastink A, Vreeken C, Nivard MJM, Searles LL, Vogel EW (1989) Sequence analysis of N-ethyl-N-nitrosourea-induced vermilion mutations in Drosophila melanogaster. Genetics 123:123–129

    Google Scholar 

  • Pastink A, Heemskerk E, Nivard MJM, Van Vliet CJ, Vogel EW (1991) Mutational specificity of ethyl methanesulfonate in excision-repair-proficient and -deficient strains of Drosophila melanogaster. Mol Gen Genet 229:213–218

    Google Scholar 

  • Saffhill R (1985) In vitro miscoding of alkylthymines with DNA and RNA polymerases. Chem -Biol Interact 53:121–130

    Google Scholar 

  • Saffhill R, Margison GP, O'Connor PJ (1985) Mechanisms of carcinogenesis induced by alkylating agents. Biochim Biophys Acta 823:111–145

    Google Scholar 

  • Saiki RR, Scharf S, Faloona F, Mullis KB, Horn GT, Ehrlich HA, Arnheim N (1985) Enzymatic amplification of α-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354

    Google Scholar 

  • Saiki RR, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Ehrlich HA (1988) Primer-directed enzymatic amplification of DNA with a thermostable polymerase. Science 239:487–591

    Google Scholar 

  • Searles LL, Voelker RA (1986) Molecular characterization of the Drosophila vermilion locus and its suppressible alleles. Proc Natl Acad Sci USA 83:404–408

    Google Scholar 

  • Searles LL, Ruth RS, Pret A, Fridell RA, Ali AJ (1990) Structure and transcription of the Drosophila melanogaster vermilion gene and several mutant alleles. Mol Cell Biol 10:1423–1431

    Google Scholar 

  • Sierra LM, Nivard MJM, Pastink A, Vogel EW (1989) Isolation and molecular characterization of mutations induced by diethylnitrosamine and diethylsulphate in Drosophila melanogaster. Environ Mol Mutagen 14, Suppl 15:186

    Google Scholar 

  • Singer B (1976) All oxygens in nucleic acids react with carcinogenic ethylating agents. Nature (London) 264:333–339

    Google Scholar 

  • Singer B, Grunberger D (1983) Molecular biology of mutagens and carcinogens. Plenum Press, New York

    Google Scholar 

  • Singer B, Sagi J, Kusmierek JT (1983) Escherichia coli polymerase I can use O2-methyldeoxythymidine or O4-methyldeoxythymidine in place of deoxythymidine in primed poly (dA-dT)·(poly (dA-dT) synthesis. Proc Natl Acad Sci USA 80:4584–4588

    Google Scholar 

  • Sun L, Singer B (1975) The specificity of different classes of ethylating agents towards various sites of HeLa cell DNA in vitro and in vivo. Biochemistry 14:1795–1802

    Google Scholar 

  • Swain CG, Scott CB (1953) Quantitative correlation of relative rates. Comparison of hydroxide ion with nucleophilic reagents towards alkyl halides, esters, epoxides and acyl halides. J Am Chem Soc 75:141–147

    Google Scholar 

  • Van Zeeland AA (1988) Molecular dosimetry of alkylating agents: quantitative comparison of genetic effects on the basis of DNA adduct formation. Mutagenesis 3:179–191

    Google Scholar 

  • Van Zeeland AA, De Groot A, Neuhäuser-Klaus A (1990) DNA adduct formation in mouse testis by ethylating agents: a comparison with germ-cell mutagenesis. Mutat Res 231:55–62

    Google Scholar 

  • Vitelli A, Di Muccio A, Calcagnile A, Zapponi GA, Bignami M, Dogliotti E (1989) The origin of DNA single strand breaks induced by ethylating agents in mammalian cells. Annali Istituto Superiore di Sanita 25:51–55

    Google Scholar 

  • Vogel EW, Natarajan AT (1982) The relation between reaction kinetics and mutagenic action of mono-functional alkylating agents in higher eukaryotic systems. III. Interspecies comparisons. In: de Serres FJ, Hollaender A, (eds.) Chemical Mutagens, vol. 7. Plenum Press, New York, pp 295–336

    Google Scholar 

  • Walker AR, Howells AJ, Tearle RG (1986) Cloning and characterization of the vermilion gene of Drosophila melanogaster. Mol Gen Genet 202:102–107

    Google Scholar 

  • Yanisch-Perron C, Vieira J, Messing J (1985) Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene 33:103–119

    Google Scholar 

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Author notes

  1. Luisa María Sierra

    Present address: Area de Genética, Departamento de Biología Funcional, Universidad de Oviedo, E-33071, Oviedo, Spain

Authors and Affiliations

  1. Department of Radiation Genetics and Chemical Mutagenesis, Sylvius Laboratory, State University of Leiden, NL-2333AL, Leiden, The Netherlands

    Luisa María Sierra, Albert Pastink, Madeleine JM Nivard & Ekkehart W. Vogel

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  1. Luisa María Sierra
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  2. Albert Pastink
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  3. Madeleine JM Nivard
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  4. Ekkehart W. Vogel
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Communicated by B.J. Kilbey

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Sierra, L.M., Pastink, A., Nivard, M.J. et al. DNA base sequence changes induced by diethyl sulfate in postmeiotic male germ cells of Drosophila melanogaster . Molec. Gen. Genet. 237, 370–374 (1993). https://doi.org/10.1007/BF00279440

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