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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
. 1992 Jan 1;89(1):368–372. doi: 10.1073/pnas.89.1.368

Mutagenic specificities of four stereoisomeric benzo[c]phenanthrene dihydrodiol epoxides.

C A Bigger 1, J St John 1, H Yagi 1, D M Jerina 1, A Dipple 1
PMCID: PMC48238  PMID: 1729707

Abstract

The pS189 shuttle vector carrying a supF target gene was used to compare the mutagenic specificities of the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide. One of these isomers is the most tumorigenic dihydrodiol epoxide tested to date and another is essentially inactive as a tumorigen. Overall mutagenicities were not correlated with tumorigenicities, but each configurational isomer induced a unique spectrum of mutational hot spots in the supF target gene, which monitors primarily point mutations. It is suggested that the demonstrated isomer-specific selectivity for mutation targets within the supF gene may be indicative of a similar selectivity for one gene versus another and that such selectivity may be one determinant of relative tumorigenicity.

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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. EVIDENCE FOR THE BINDING OF POLYNUCLEAR AROMATIC HYDROCARBONS TO THE NUCLEIC ACIDS OF MOUSE SKIN: RELATION BETWEEN CARCINOGENIC POWER OF HYDROCARBONS AND THEIR BINDING TO DEOXYRIBONUCLEIC ACID. Nature. 1964 May 23;202:781–784. doi: 10.1038/202781a0. [DOI] [PubMed] [Google Scholar]
  2. Barbacid M. Oncogenes and human cancer: cause or consequence? Carcinogenesis. 1986 Jul;7(7):1037–1042. doi: 10.1093/carcin/7.7.1037. [DOI] [PubMed] [Google Scholar]
  3. Bigger C. A., Flickinger D. J., St John J., Harvey R. G., Dipple A. Preferential mutagenesis at G.C base pairs by the anti 3,4-dihydrodiol 1,2-epoxide of 7-methylbenz[a]anthracene. Mol Carcinog. 1991;4(3):176–179. doi: 10.1002/mc.2940040303. [DOI] [PubMed] [Google Scholar]
  4. Bigger C. A., Strandberg J., Yagi H., Jerina D. M., Dipple A. Mutagenic specificity of a potent carcinogen, benzo[c]phenanthrene (4R,3S)-dihydrodiol (2S,1R)-epoxide, which reacts with adenine and guanine in DNA. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2291–2295. doi: 10.1073/pnas.86.7.2291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carothers A. M., Urlaub G., Mucha J., Harvey R. G., Chasin L. A., Grunberger D. Splicing mutations in the CHO DHFR gene preferentially induced by (+/-)-3 alpha,4 beta-dihydroxy-1 alpha,2 alpha-epoxy-1,2,3,4- tetrahydrobenzo[c]phenanthrene. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5464–5468. doi: 10.1073/pnas.87.14.5464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dipple A., Pigott M. A., Agarwal S. K., Yagi H., Sayer J. M., Jerina D. M. Optically active benzo[c]phenanthrene diol epoxides bind extensively to adenine in DNA. Nature. 1987 Jun 11;327(6122):535–536. doi: 10.1038/327535a0. [DOI] [PubMed] [Google Scholar]
  7. Drinkwater N. R., Klinedinst D. K. Chemically induced mutagenesis in a shuttle vector with a low-background mutant frequency. Proc Natl Acad Sci U S A. 1986 May;83(10):3402–3406. doi: 10.1073/pnas.83.10.3402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DuBridge R. B., Tang P., Hsia H. C., Leong P. M., Miller J. H., Calos M. P. Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system. Mol Cell Biol. 1987 Jan;7(1):379–387. doi: 10.1128/mcb.7.1.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Graham F. L., Smiley J., Russell W. C., Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977 Jul;36(1):59–74. doi: 10.1099/0022-1317-36-1-59. [DOI] [PubMed] [Google Scholar]
  10. Kraemer K. H., Seidman M. M. Use of supF, an Escherichia coli tyrosine suppressor tRNA gene, as a mutagenic target in shuttle-vector plasmids. Mutat Res. 1989 Mar-May;220(2-3):61–72. doi: 10.1016/0165-1110(89)90011-0. [DOI] [PubMed] [Google Scholar]
  11. Kunkel T. A. Mutational specificity of depurination. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1494–1498. doi: 10.1073/pnas.81.5.1494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Levin W., Chang R. L., Wood A. W., Thakker D. R., Yagi H., Jerina D. M., Conney A. H. Tumorigenicity of optical isomers of the diastereomeric bay-region 3,4-diol-1,2-epoxides of benzo(c)phenanthrene in murine tumor models. Cancer Res. 1986 May;46(5):2257–2261. [PubMed] [Google Scholar]
  13. Quintanilla M., Brown K., Ramsden M., Balmain A. Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature. 1986 Jul 3;322(6074):78–80. doi: 10.1038/322078a0. [DOI] [PubMed] [Google Scholar]
  14. Reardon D. B., Bigger C. A., Dipple A. DNA polymerase action on bulky deoxyguanosine and deoxyadenosine adducts. Carcinogenesis. 1990 Jan;11(1):165–168. doi: 10.1093/carcin/11.1.165. [DOI] [PubMed] [Google Scholar]
  15. Seidman M. M., Dixon K., Razzaque A., Zagursky R. J., Berman M. L. A shuttle vector plasmid for studying carcinogen-induced point mutations in mammalian cells. Gene. 1985;38(1-3):233–237. doi: 10.1016/0378-1119(85)90222-7. [DOI] [PubMed] [Google Scholar]
  16. Seidman M. The development of transient SV40 based shuttle vectors for mutagenesis studies: problems and solutions. Mutat Res. 1989 Mar-May;220(2-3):55–60. doi: 10.1016/0165-1110(89)90010-9. [DOI] [PubMed] [Google Scholar]
  17. Sims P., Grover P. L., Swaisland A., Pal K., Hewer A. Metabolic activation of benzo(a)pyrene proceeds by a diol-epoxide. Nature. 1974 Nov 22;252(5481):326–328. doi: 10.1038/252326a0. [DOI] [PubMed] [Google Scholar]
  18. Strauss B. S. Cellular aspects of DNA repair. Adv Cancer Res. 1985;45:45–105. doi: 10.1016/s0065-230x(08)60266-3. [DOI] [PubMed] [Google Scholar]
  19. Wang P., Bennett R. A., Povirk L. F. Melphalan-induced mutagenesis in an SV40-based shuttle vector: predominance of A.T----T.A transversions. Cancer Res. 1990 Dec 1;50(23):7527–7531. [PubMed] [Google Scholar]
  20. Wood A. W., Chang R. L., Levin W., Thakker D. R., Yagi H., Sayer J. M., Jerina D. M., Conney A. H. Mutagenicity of the enantiomers of the diastereomeric bay-region benzo(c)phenanthrene 3,4-diol-1,2-epoxides in bacterial and mammalian cells. Cancer Res. 1984 Jun;44(6):2320–2324. [PubMed] [Google Scholar]

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