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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
. 1976 Jan;73(1):243–247. doi: 10.1073/pnas.73.1.243

Carcinogenicity of benzo[a]pyrene 4,5-, 7,8-, and 9,10-oxides on mouse skin.

W Levin, A W Wood, H Yagi, P M Dansette, D M Jerina, A H Conney
PMCID: PMC335877  PMID: 1061121

Abstract

Benzo[a]pyrene and three arene oxides of benzo[a]pyrene (benzo[a]pyrene 4,5-, 7,8-, and 9,10-oxides) have been tested for carcinogenicity in mice by topical application of each compound (0.1 or 0.4 mumol) once every 2 weeks for 60 weeks. At the high dose, benzo[a]pyrene and the 7,8-oxide were highly carcinogenic, whereas the 4,5-oxide (K-region oxide) was weakly active and the 9,10-oxide was inactive. At the low dose, only benzo[a]pyrene was highly carcinogenic. The carcinogenic activities of the three arene oxides of benzo[a]pyrene were not correlated with their stabilities or mutagenic activities.

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Selected References

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  1. Ames B. N., Durston W. E., Yamasaki E., Lee F. D. Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2281–2285. doi: 10.1073/pnas.70.8.2281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ames B. N., Sims P., Grover P. L. Epoxides of carcinogenic polycyclic hydrocarbons are frameshift mutagens. Science. 1972 Apr 7;176(4030):47–49. doi: 10.1126/science.176.4030.47. [DOI] [PubMed] [Google Scholar]
  3. Borgen A., Darvey H., Castagnoli N., Crocker T. T., Rasmussen R. E., Wang I. Y. Metabolic conversion of benzo(a)pyrene by Syrian hamster liver microsomes and binding of metabolites to deoxyribonucleic acid. J Med Chem. 1973 May;16(5):502–506. doi: 10.1021/jm00263a020. [DOI] [PubMed] [Google Scholar]
  4. Boyland E., Sims P. The carcinogenic activities in mice of compounds related to benz[a]anthracene. Int J Cancer. 1967 Sep 15;2(5):500–504. doi: 10.1002/ijc.2910020511. [DOI] [PubMed] [Google Scholar]
  5. Boyland E. The correlation of experimental carcinogenesis and cancer in man. Prog Exp Tumor Res. 1969;11:222–234. doi: 10.1159/000391396. [DOI] [PubMed] [Google Scholar]
  6. Bürki K., Wheeler J. E., Akamatsu Y., Scribner J. E., Candelas G., Bresnick E. Early differential effects of 3-methylcholanthrene and its "K-region" epoxide on mouse skin. Possible implication in the two-stage mechanism of tumorigenesis. J Natl Cancer Inst. 1974 Oct;53(4):967–976. doi: 10.1093/jnci/53.4.967. [DOI] [PubMed] [Google Scholar]
  7. DELLA PORTA G., TERRACINI B., DAMMERT K., SHUBIK P. Histopathology of tumors induced in mice treated with polyoxyethylene sorbitan monostearate. J Natl Cancer Inst. 1960 Sep;25:573–605. [PubMed] [Google Scholar]
  8. Dansette P., Jerina D. M. A facile synthesis of arene oxides at the K regions of polycylic hydrocarbons. J Am Chem Soc. 1974 Feb 20;96(4):1224–1225. doi: 10.1021/ja00811a046. [DOI] [PubMed] [Google Scholar]
  9. Epstein S. S. Environmental determinants of human cancer. Cancer Res. 1974 Oct;34(10):2425–2435. [PubMed] [Google Scholar]
  10. Gelboin H. V., Kinoshita N., Wiebel F. J. Microsomal hydroxylases: induction and role in polycyclic hydrocarbon carcinogenesis and toxicity. Fed Proc. 1972 Jul-Aug;31(4):1298–1309. [PubMed] [Google Scholar]
  11. Grover P. L., Sims P., Huberman E., Marquardt H., Kuroki T., Heidelberger C. In vitro transformation of rodent cells by K-region derivatives of polycyclic hydrocarbons. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1098–1101. doi: 10.1073/pnas.68.6.1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grover P. L., Sims P., Mitchley B. C., Roe F. J. The carcinogenicity of polycyclic hydrocarbon epoxides in newborn mice. Br J Cancer. 1975 Feb;31(2):182–188. doi: 10.1038/bjc.1975.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Huberman E., Aspiras L., Heidelberger C., Grover P. L., Sims P. Mutagenicity to mammalian cells of epoxides and other derivatives of polycyclic hydrocarbons. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3195–3199. doi: 10.1073/pnas.68.12.3195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huberman E., Kuroki T., Marquardt H., Selkirk J. K., Heidelberger C., Grover P. L., Sims P. Transformation of hamster embryo cells by epoxides and other derivatives of polycyclic hydrocarbons. Cancer Res. 1972 Jul;32(7):1391–1396. [PubMed] [Google Scholar]
  15. Huberman E., Sachs L. Cell-mediated mutagenesis of mammalian cells with chemical carcinogens. Int J Cancer. 1974 Mar 15;13(3):326–333. doi: 10.1002/ijc.2910130308. [DOI] [PubMed] [Google Scholar]
  16. Jerina D. M., Daly J. W. Arene oxides: a new aspect of drug metabolism. Science. 1974 Aug 16;185(4151):573–582. doi: 10.1126/science.185.4151.573. [DOI] [PubMed] [Google Scholar]
  17. Marquardt H., Kuroki T., Huberman E., Selkirk J. K., Heidelberger C., Grover P. L., Sims P. Malignant transformation of cells derived from mouse prostate by epoxides and other derivatives of polycyclic hydrocarbons. Cancer Res. 1972 Apr;32(4):716–720. [PubMed] [Google Scholar]
  18. Marquardt H., Sodergren J. E., Sims P., Grover P. L. Malignant transformation in vitro of mouse fibroblasts by 7,12-dimethylbenz(A)anthracene and 7-hydroxymethylbenz(A)anthracene and by their K-region derivatives. Int J Cancer. 1974 Mar 15;13(3):304–310. doi: 10.1002/ijc.2910130305. [DOI] [PubMed] [Google Scholar]
  19. Miller E. C., Miller J. A. Low carcinogenicity of the K-region epoxides of 7-methylbenz(a)-anthracene and benz(a)anthracene in the mouse and rat. Proc Soc Exp Biol Med. 1967 Mar;124(3):915–919. doi: 10.3181/00379727-124-31885. [DOI] [PubMed] [Google Scholar]
  20. Miller J. A. Carcinogenesis by chemicals: an overview--G. H. A. Clowes memorial lecture. Cancer Res. 1970 Mar;30(3):559–576. [PubMed] [Google Scholar]
  21. Sims P., Grover P. L. Epoxides in polycyclic aromatic hydrocarbon metabolism and carcinogenesis. Adv Cancer Res. 1974;20:165–274. doi: 10.1016/s0065-230x(08)60111-6. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Sims P. The carcinogenic activities in mice of compounds related to 3-methylcholanthrene. Int J Cancer. 1967 Sep 15;2(5):505–508. doi: 10.1002/ijc.2910020512. [DOI] [PubMed] [Google Scholar]
  24. Wood A. W., Goode R. L., Chang R. L., Levin W., Conney A. H., Yagi H., Dansette P. M., Jerina D. M. Mutagenic and cytotoxic activity of benzol[a]pyrene 4,5-, 7,8-, and 9,10-oxides and the six corresponding phenols. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3176–3180. doi: 10.1073/pnas.72.8.3176. [DOI] [PMC free article] [PubMed] [Google Scholar]

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