Abstract
Three pyrenofurans, the pyreno[1,2-b]furan (FP1), the pyreno[2,1-b] furan (FP2) and the pyreno[4,5-b]furan (FP3) have been synthesized as analogues of the mutagenic and carcinogenic benzo(a)pyrene (FP1 and FP2) and of its non-carcinogenic isomer benzo(e)pyrene (FP3). For each of the pyrenofurans, the reactivity with DNA has been tested in presence of liver microsomes of rats induced with 3-methylcholanthrene. Fluorescence spectroscopy showed that only FP2 and FP3 which possess a "bay region" react with DNA. In both cases, metabolites bound to DNA have a fluorescence emission comparable to that of the "bay region" dihydrodiols obtained after the "in vitro" metabolism of initial molecules. FP2 is shown to react similarly to benzo(a)pyrene whereas the reactivity of FP3 is different from that of benzo(e)pyrene, in spite of their structural similarities. This is probably due to reasons of three-dimensional space configuration. The peculiar reactivity of FP3 is predicted by calculations of the bond order values.
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Selected References
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- Daudel P., Duquesne M., Vigny P., Grover P. L., Sims P. Fluorescence spectral evidence that benzo(a)pyrene-DNA products in mouse skin arise from diol-epoxides. FEBS Lett. 1975 Oct 1;57(3):250–253. doi: 10.1016/0014-5793(75)80310-3. [DOI] [PubMed] [Google Scholar]
- Gelboin H. V. A microsome-dependent binding of benzo[a]pyrene to DNA. Cancer Res. 1969 Jun;29(6):1272–1276. [PubMed] [Google Scholar]
- Hartree E. F. Determination of protein: a modification of the Lowry method that gives a linear photometric response. Anal Biochem. 1972 Aug;48(2):422–427. doi: 10.1016/0003-2697(72)90094-2. [DOI] [PubMed] [Google Scholar]
- Kapitulnik J., Wislocki P. G., Levin W., Yagi H., Jerina D. M., Conney A. H. Tumorigenicity studies with diol-epoxides of benzo(a)pyrene which indicate that (+/-)-trans-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene is an ultimate carcinogen in newborn mice. Cancer Res. 1978 Feb;38(2):354–358. [PubMed] [Google Scholar]
- 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]