Skip NavigationSkip to Content

Metabolic activation of 4H-cyclopenta

  1. Author:
    Agarwal, R.
    Coffing, S. L.
    Baird, W. M.
    Harvey, R. G.
    Dipple, A.
  2. Author Address

    Agarwal R NCI, Expt Carcinogenesis Lab Bldg 37,Room 3C28 Bethesda, MD 20892 USA NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program Frederick, MD 21702 USA Purdue Univ, Ctr Canc W Lafayette, IN 47907 USA Univ Chicago, Ben May Inst Chicago, IL 60637 USA
    1. Year: 1999
  1. Journal: Chemical Research in Toxicology
    1. 12
    2. 5
    3. Pages: 437-441
  2. Type of Article: Article
  1. Abstract:

    The tumor initiating activities of 4H-cyclopenta[def]chrysene (C[def]C) and its two putative reactive metabolites. trans-1,2-dihydroxy-anti-3,3a-epoxy-1,2,3,3a-tetrahydro-4H-cyclopent a [def]chrysene (C[def]C-3,3a-DE) and trans-6,7-dihydroxy-anti-8,9-epoxy-6,7,8,9-tetrahydro-4H-cyclopenta[ def]chrysene (C[def]C-8,9-DE), were evaluated previously in mice [Amin, S., et al. (1995) Carcinogenesis 16, 2813-2817]. C[def]C-3,3a-DE was the more active inducer of lung tumors and elicited twice as many tumors as C[def]C-8,9-DE. In this study, the route of metabolism of C[def]C to DNA-reactive metabolites in the human mammary carcinoma cell line (MCF-7) was investigated using the P-32-postlabeling assay. The results show that metabolic activation to DNA-binding species proceeds through the formation of both trans-1,2-dihydrodiol and trans-6,7-dihydrodiol metabolites of C[def]C. At a 1 mu M dose, adducts from the methylene-bridged (C[def]C-3,3a-DE) and bay region (C[def]C-8,9-DE) dihydrodiol epoxides were detected in comparable amounts. In contrast, the majority of the postlabeled adducts recovered from cells exposed to a 10 mu M dose were derived from the bay region dihydrodiol epoxide, C[def]C-8,9-DE. Using markers from reactions of the dihydrodiol epoxides with deoxyguanosine 3'-phosphate and deoxyadenosine 3'-phosphate, it was shown that the major radioactive spots formed with both anti-C[def]C-3,3a-DE and anti-C[def]C-8,9-DE chromatographed with deoxyguanosine adduct markers. Thus, the human cells used in these studies can activate C[def]C to carcinogenic metabolites. [References: 32]

    See More

External Sources

  1. No sources found.

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel