Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1993 Oct;101(Suppl 3):207–212. doi: 10.1289/ehp.93101s3207

Molecular analysis of mutations induced at the hisD3052 allele of Salmonella by single chemicals and complex mixtures.

D M DeMarini 1, D A Bell 1, J G Levine 1, M L Shelton 1, A Abu-Shakra 1
PMCID: PMC1521146  PMID: 8143618

Abstract

More single chemicals and complex environmental mixtures have been evaluated for mutagenicity at the hisD3052 allele of Salmonella, primarily in strain TA98, than in any other mutation assay. The development of colony probe hybridization procedures and the application of the polymerase chain reaction and direct DNA sequencing has permitted rapid molecular access to this allele. We discuss these techniques and the resulting mutation spectra that have been induced by a variety of environmental mutagens and complex mixtures. A common GC or CG deletion within a hot-spot region of the sequence dominates most of the spectra. In addition to this two-base deletion, we have recovered about 200 other types of mutations within the 72-base target for reversion of the hisD3052 allele. These include a variety of deletions (as large as 35 bases), duplications (as large as 46 bases), and complex mutations involving base substitutions. The quasipalindromic nature of the target sequence and its potential to form DNA secondary structures and slippage mismatches appear to be an important basis for the mutability of this allele.

Full text

PDF
210

Selected References

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

  1. Ariza R. R., Serrano A., Pueyo C. Direct-acting mutagenic activity in white, rosé, and red wines with the Ara test of Salmonella typhimurium. Environ Mol Mutagen. 1992;19(1):14–20. doi: 10.1002/em.2850190104. [DOI] [PubMed] [Google Scholar]
  2. Ariza R. R., Serrano A., Pueyo C. Direct-acting mutagenic activity in white, rosé, and red wines with the Ara test of Salmonella typhimurium. Environ Mol Mutagen. 1992;19(1):14–20. doi: 10.1002/em.2850190104. [DOI] [PubMed] [Google Scholar]
  3. Atkins J. F., Weiss R. B., Thompson S., Gesteland R. F. Towards a genetic dissection of the basis of triplet decoding, and its natural subversion: programmed reading frame shifts and hops. Annu Rev Genet. 1991;25:201–228. doi: 10.1146/annurev.ge.25.120191.001221. [DOI] [PubMed] [Google Scholar]
  4. Bell D. A., DeMarini D. M. Excessive cycling converts PCR products to random-length higher molecular weight fragments. Nucleic Acids Res. 1991 Sep 25;19(18):5079–5079. doi: 10.1093/nar/19.18.5079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bell D. A., Levine J. G., DeMarini D. M. DNA sequence analysis of revertants of the hisD3052 allele of Salmonella typhimurium TA98 using the polymerase chain reaction and direct sequencing: application to 1-nitropyrene-induced revertants. Mutat Res. 1991 Feb;252(1):35–44. doi: 10.1016/0165-1161(91)90249-8. [DOI] [PubMed] [Google Scholar]
  6. Cebula T. A., Koch W. H. Sequence analysis of Salmonella typhimurium revertants. Prog Clin Biol Res. 1990;340D:367–377. [PubMed] [Google Scholar]
  7. DeMarini D. M., Abu-Shakra A., Gupta R., Hendee L. J., Levine J. G. Molecular analysis of mutations induced by the intercalating agent ellipticine at the hisD3052 allele of Salmonella typhimurium TA98. Environ Mol Mutagen. 1992;20(1):12–18. doi: 10.1002/em.2850200104. [DOI] [PubMed] [Google Scholar]
  8. DeMarini D. M., Fuscoe J. C. Workshop overview: new molecular techniques in genome analysis. Environ Mol Mutagen. 1991;18(4):222–223. doi: 10.1002/em.2850180403. [DOI] [PubMed] [Google Scholar]
  9. DeMarini D. M. Genotoxicity of tobacco smoke and tobacco smoke condensate. Mutat Res. 1983 Jan;114(1):59–89. doi: 10.1016/0165-1110(83)90019-2. [DOI] [PubMed] [Google Scholar]
  10. Fuscoe J. C., Wu R., Shen N. H., Healy S. K., Felton J. S. Base-change analysis of revertants of the hisD3052 allele in Salmonella typhimurium. Mutat Res. 1988 Sep;201(1):241–251. doi: 10.1016/0027-5107(88)90131-5. [DOI] [PubMed] [Google Scholar]
  11. Hartman P. E., Ames B. N., Roth J. R., Barnes W. M., Levin D. E. Target sequences for mutagenesis in Salmonella histidine-requiring mutants. Environ Mutagen. 1986;8(4):631–641. doi: 10.1002/em.2860080414. [DOI] [PubMed] [Google Scholar]
  12. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  13. Houk V. S. The genotoxicity of industrial wastes and effluents. Mutat Res. 1992 Aug;277(2):91–138. doi: 10.1016/0165-1110(92)90001-p. [DOI] [PubMed] [Google Scholar]
  14. Isono K., Yourno J. Chemical carcinogens as frameshift mutagens: Salmonella DNA sequence sensitive to mutagenesis by polycyclic carcinogens. Proc Natl Acad Sci U S A. 1974 May;71(5):1612–1617. doi: 10.1073/pnas.71.5.1612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kier L. D., Yamasaki E., Ames B. N. Detection of mutagenic activity in cigarette smoke condensates. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4159–4163. doi: 10.1073/pnas.71.10.4159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kupchella E., Cebula T. A. Analysis of Salmonella typhimurium hisD3052 revertants: the use of oligodeoxyribonucleotide colony hybridization, PCR, and direct sequencing in mutational analysis. Environ Mol Mutagen. 1991;18(4):224–230. doi: 10.1002/em.2850180404. [DOI] [PubMed] [Google Scholar]
  17. Lewtas J. Genotoxicity of complex mixtures: strategies for the identification and comparative assessment of airborne mutagens and carcinogens from combustion sources. Fundam Appl Toxicol. 1988 May;10(4):571–589. doi: 10.1016/0272-0590(88)90184-4. [DOI] [PubMed] [Google Scholar]
  18. Maron D. M., Ames B. N. Revised methods for the Salmonella mutagenicity test. Mutat Res. 1983 May;113(3-4):173–215. doi: 10.1016/0165-1161(83)90010-9. [DOI] [PubMed] [Google Scholar]
  19. Mumford J. L., He X. Z., Chapman R. S., Cao S. R., Harris D. B., Li X. M., Xian Y. L., Jiang W. Z., Xu C. W., Chuang J. C. Lung cancer and indoor air pollution in Xuan Wei, China. Science. 1987 Jan 9;235(4785):217–220. doi: 10.1126/science.3798109. [DOI] [PubMed] [Google Scholar]
  20. O'Hara S. M., Marnett L. J. DNA sequence analysis of spontaneous and beta-methoxy-acrolein-induced mutations in Salmonella typhimurium hisD3052. Mutat Res. 1991 Mar;247(1):45–56. doi: 10.1016/0027-5107(91)90032-j. [DOI] [PubMed] [Google Scholar]
  21. Oeschger N. S., Hartman P. E. ICR-induced frameshift mutations in the histidine operon of Salmonella. J Bacteriol. 1970 Feb;101(2):490–504. doi: 10.1128/jb.101.2.490-504.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reynolds S. H., Anderson M. W. Activation of proto-oncogenes in human and mouse lung tumors. Environ Health Perspect. 1991 Jun;93:145–148. doi: 10.1289/ehp.9193145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reynolds S. H., Anna C. K., Brown K. C., Wiest J. S., Beattie E. J., Pero R. W., Iglehart J. D., Anderson M. W. Activated protooncogenes in human lung tumors from smokers. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1085–1089. doi: 10.1073/pnas.88.4.1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ripley L. S. Frameshift mutation: determinants of specificity. Annu Rev Genet. 1990;24:189–213. doi: 10.1146/annurev.ge.24.120190.001201. [DOI] [PubMed] [Google Scholar]
  25. Streisinger G., Okada Y., Emrich J., Newton J., Tsugita A., Terzaghi E., Inouye M. Frameshift mutations and the genetic code. This paper is dedicated to Professor Theodosius Dobzhansky on the occasion of his 66th birthday. Cold Spring Harb Symp Quant Biol. 1966;31:77–84. doi: 10.1101/sqb.1966.031.01.014. [DOI] [PubMed] [Google Scholar]
  26. Watts R. R., Lemieux P. M., Grote R. A., Lowans R. W., Williams R. W., Brooks L. R., Warren S. H., DeMarini D. M., Bell D. A., Lewtas J. Development of source testing, analytical, and mutagenicity bioassay procedures for evaluating emissions from municipal and hospital waste combustors. Environ Health Perspect. 1992 Nov;98:227–234. doi: 10.1289/ehp.9298227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zeiger E., Risko K. J., Margolin B. H. Strategies to reduce the cost of mutagenicity screening with the Salmonella assay. Environ Mutagen. 1985;7(6):901–911. doi: 10.1002/em.2860070611. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES