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
. 1985 Oct;82(20):7076–7080. doi: 10.1073/pnas.82.20.7076

Site-specific carcinogen binding to DNA in polytene chromosomes.

P D Kurth, M Bustin
PMCID: PMC391313  PMID: 3931083

Abstract

Treatment of Chironomus polytene chromosomes with the ultimate carcinogen benzo[a]pyrene diol epoxide I or in vivo administration of the parent hydrocarbon to larvae indicates that the carcinogen interacts with the genome in a nonrandom manner. Visualization of the carcinogen-DNA binding sites by immunofluorescence reveals that, in vivo, some sites are preferentially modified. The combined effects of DNA sequence, chromatin structure, and gene localization may lead to selective targeting of carcinogens to specific genomic regions. In polytene chromosomes the targeting effect is amplified, thereby making these chromosomes a uniquely suitable system for visualizing and studying site-specific interactions of carcinogens with the genome.

Full text

PDF
7076

Images in this article

7077Image
on p.7077
7077Image
on p.7077
7078Image
on p.7078
7078Image
on p.7078
7078Image
on p.7078
7078Image
on p.7078
7078Image
on p.7078
7078Image
on p.7078
7079Image
on p.7079
7079Image
on p.7079
7079Image
on p.7079
7079Image
on p.7079
7079Image
on p.7079

Selected References

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

  1. Bailey G. S., Nixon J. E., Hendricks J. D., Sinnhuber R. O., Van Holde K. E. Carcinogen aflatoxin B1 is located preferentially in internucleosomal deoxyribonucleic acid following exposure in vivo in rainbow trout. Biochemistry. 1980 Dec 9;19(25):5836–5842. doi: 10.1021/bi00566a027. [DOI] [PubMed] [Google Scholar]
  2. Beard P., Kaneko M., Cerutti P. N-Acetoxy-acetylaminofluorene reacts preferentially with a control region of intracellular SV40 chromosome. Nature. 1981 May 7;291(5810):84–85. doi: 10.1038/291084a0. [DOI] [PubMed] [Google Scholar]
  3. Boles T. C., Hogan M. E. Site-specific carcinogen binding to DNA. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5623–5627. doi: 10.1073/pnas.81.18.5623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Comings O. E., Kovacs B. W., Avelino E., Harris D. C. Mechanisms of chromosome banding. V. Quinacrine banding. Chromosoma. 1975;50(2):111–114. doi: 10.1007/BF00283236. [DOI] [PubMed] [Google Scholar]
  5. Gelboin H. V. Benzo[alpha]pyrene metabolism, activation and carcinogenesis: role and regulation of mixed-function oxidases and related enzymes. Physiol Rev. 1980 Oct;60(4):1107–1166. doi: 10.1152/physrev.1980.60.4.1107. [DOI] [PubMed] [Google Scholar]
  6. Guerrero I., Calzada P., Mayer A., Pellicer A. A molecular approach to leukemogenesis: mouse lymphomas contain an activated c-ras oncogene. Proc Natl Acad Sci U S A. 1984 Jan;81(1):202–205. doi: 10.1073/pnas.81.1.202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Guerrero I., Villasante A., Corces V., Pellicer A. Activation of a c-K-ras oncogene by somatic mutation in mouse lymphomas induced by gamma radiation. Science. 1984 Sep 14;225(4667):1159–1162. doi: 10.1126/science.6474169. [DOI] [PubMed] [Google Scholar]
  8. Irvin T. R., Wogan G. N. Quantitation of aflatoxin B1 adduction within the ribosomal RNA gene sequences of rat liver DNA. Proc Natl Acad Sci U S A. 1984 Feb;81(3):664–668. doi: 10.1073/pnas.81.3.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jack P. L., Brookes P. The distribution of benzo(a)pyrene DNA adducts in mammalian chromatin. Nucleic Acids Res. 1981 Nov 11;9(21):5533–5552. doi: 10.1093/nar/9.21.5533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kennedy A. R., Cairns J., Little J. B. Timing of the steps in transformation of C3H 10T 1/2 cells by X-irradiation. Nature. 1984 Jan 5;307(5946):85–86. doi: 10.1038/307085a0. [DOI] [PubMed] [Google Scholar]
  11. Kootstra A., Slaga T. J., Olins D. E. Interaction of benzo[alpha]pyrene diol-epoxide with nuclei and isolated chromatin. Chem Biol Interact. 1979 Dec;28(2-3):225–236. doi: 10.1016/0009-2797(79)90163-7. [DOI] [PubMed] [Google Scholar]
  12. Koreeda M., Moore P. D., Wislocki P. G., Levin W., Yagi H., Jerina D. M. Binding of benzo[a]pyrene 7,8-diol-9,10-epoxides to DNA, RNA, and protein of mouse skin occurs with high stereoselectivity. Science. 1978 Feb 17;199(4330):778–781. doi: 10.1126/science.622566. [DOI] [PubMed] [Google Scholar]
  13. Kuroki T., Heidelberger C. The binding of polycyclic aromatic hydrocarbons to the DNA, RNA, and proteins of transformable cells in culture. Cancer Res. 1971 Dec;31(12):2168–2176. [PubMed] [Google Scholar]
  14. Kurth P. D., Reisch J. C., Bustin M. Selective exposure of antigenic determinants in chromosomal proteins upon gene activation in polytene chromosomes. Exp Cell Res. 1983 Feb;143(2):257–269. doi: 10.1016/0014-4827(83)90051-4. [DOI] [PubMed] [Google Scholar]
  15. Land H., Parada L. F., Weinberg R. A. Cellular oncogenes and multistep carcinogenesis. Science. 1983 Nov 18;222(4625):771–778. doi: 10.1126/science.6356358. [DOI] [PubMed] [Google Scholar]
  16. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  17. Lo K., Kakunaga T. Only one type of benzo(a) pyrene-DNA adduct is detected in transformable mouse cells. Biochem Biophys Res Commun. 1981 Apr 15;99(3):820–829. doi: 10.1016/0006-291x(81)91238-9. [DOI] [PubMed] [Google Scholar]
  18. Marshall C. J., Vousden K. H., Phillips D. H. Activation of c-Ha-ras-1 proto-oncogene by in vitro modification with a chemical carcinogen, benzo(a)pyrene diol-epoxide. Nature. 1984 Aug 16;310(5978):586–589. doi: 10.1038/310586a0. [DOI] [PubMed] [Google Scholar]
  19. McCann J., Choi E., Yamasaki E., Ames B. N. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5135–5139. doi: 10.1073/pnas.72.12.5135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miller E. C. Some current perspectives on chemical carcinogenesis in humans and experimental animals: Presidential Address. Cancer Res. 1978 Jun;38(6):1479–1496. [PubMed] [Google Scholar]
  21. Mirkovitch J., Mirault M. E., Laemmli U. K. Organization of the higher-order chromatin loop: specific DNA attachment sites on nuclear scaffold. Cell. 1984 Nov;39(1):223–232. doi: 10.1016/0092-8674(84)90208-3. [DOI] [PubMed] [Google Scholar]
  22. Muench K. F., Misra R. P., Humayun M. Z. Sequence specificity in aflatoxin B1--DNA interactions. Proc Natl Acad Sci U S A. 1983 Jan;80(1):6–10. doi: 10.1073/pnas.80.1.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nebert D. W., Gelboin H. V. Substrate-inducible microsomal aryl hydroxylase in mammalian cell culture. I. Assay and properties of induced enzyme. J Biol Chem. 1968 Dec 10;243(23):6242–6249. [PubMed] [Google Scholar]
  24. Poirier M. C., Santella R., Weinstein I. B., Grunberger D., Yuspa S. H. Quantitation of benzo(a)pyrene-deoxyguanosine adducts by radioimmunoassay. Cancer Res. 1980 Feb;40(2):412–416. [PubMed] [Google Scholar]
  25. Robert-Nicoud M., Arndt-Jovin D. J., Zarling D. A., Jovin T. M. Immunological detection of left-handed Z DNA in isolated polytene chromosomes. Effects of ionic strength, pH, temperature and topological stress. EMBO J. 1984 Apr;3(4):721–731. doi: 10.1002/j.1460-2075.1984.tb01875.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Santos E., Martin-Zanca D., Reddy E. P., Pierotti M. A., Della Porta G., Barbacid M. Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient. Science. 1984 Feb 17;223(4637):661–664. doi: 10.1126/science.6695174. [DOI] [PubMed] [Google Scholar]
  27. Sass H., Bautz E. K. Immunoelectron microscopic localization of RNA polymerase B on isolated polytene chromosomes of Chironomus tentans. Chromosoma. 1982;85(5):633–642. doi: 10.1007/BF00330777. [DOI] [PubMed] [Google Scholar]
  28. Sass H. RNA polymerase B in polytene chromosomes: immunofluorescent and autoradiographic analysis during stimulated and repressed RNA synthesis. Cell. 1982 Feb;28(2):269–278. doi: 10.1016/0092-8674(82)90345-2. [DOI] [PubMed] [Google Scholar]
  29. Schnedl W., Breitenbach M., Stranzinger G. Mithramycin and DIPI: a pair of fluorochromes specific for GC-and AT-rich DNA respectively. Hum Genet. 1977 May 10;36(3):299–305. doi: 10.1007/BF00446280. [DOI] [PubMed] [Google Scholar]
  30. Seidman M., Mizusawa H., Slor H., Bustin M. Immunological detection of carcinogen-modified DNA fragments after in vivo modification of cellular and viral chromatin. Cancer Res. 1983 Feb;43(2):743–748. [PubMed] [Google Scholar]
  31. Seidman M., Slor H., Bustin M. The binding of a carcinogen to the nucleosomal and non-nucleosomal regions of the simian virus 40 chromosome in vivo. J Biol Chem. 1983 Apr 25;258(8):5215–5220. [PubMed] [Google Scholar]
  32. Shilo B. Z., Weinberg R. A. Unique transforming gene in carcinogen-transformed mouse cells. Nature. 1981 Feb 12;289(5798):607–609. doi: 10.1038/289607a0. [DOI] [PubMed] [Google Scholar]
  33. Slor H., Mizusawa H., Neihart N., Kakefuda T., Day R. S., 3rd, Bustin M. Immunochemical visualization of binding of the chemical carcinogen benzo(a)pyrene diol-epoxide 1 to the genome. Cancer Res. 1981 Aug;41(8):3111–3117. [PubMed] [Google Scholar]
  34. Spandidos D. A., Siminovitch L. The relationship between transformation and somatic mutation in human and Chinese hamster cells. Cell. 1978 Apr;13(4):651–662. doi: 10.1016/0092-8674(78)90215-5. [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