The binding of benzo(a)pyrene and N-methyl-N'-nitro-N-nitrosoguanidine to subnuclear fractions of AKR mouse embryo cells in culture

T. H. Zytkovicz, H. L. Moses, T. C. Spelsberg

Research output: Contribution to journalArticle

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Abstract

The marked localization of a carcinogenic polycyclic aromatic hydrocarbon, benzo(a)pyrene, and its metabolites and a carcinogenic alkylating agent, N-methyl-N'-nitro-nitrosoguanidine, to a specific subnuclear fraction (fraction I) AKR-2B mouse embryo cells in culture is described. Fraction I is isolated by sucrose gradient centrifugation of sheared nuclei from cells exposed to the carcinogens. The association of tritiated benzo(a)pyrene to fraction I consisted of loosely associated radioactivity which is extractable by organic solvents, and of tightly bound (termed 'covalently' bound) radioactivity which is not extractable by organic solvents. Increases in the extent of metabolism of benzo(a)pyrene and in the amount of 'covalently' bound radioactivity occur with increasing periods of incubation of the cells with the increasing periods of incubation of the cells with the labelled carcinogen. This observation, together with the fact that these increases are dramatically reduced by inhibiting polycyclic aromatic hydrocarbon metabolism (using the inhibitor 7,8-benzoflavone), suggests that a time-dependent metabolism of benzo(a)pyrene is required for 'covalent' binding to nuclear material. Data are presented suggesting that a two-step reaction may be involved in the binding of benzo(a)pyrene to subnuclear macromolecules. The fraction I localization of such structurally diverse chemical carcinogens as benzo(a)pyrene and N-methyl-N'-nitro-N-nitrosoguanidine suggests that this fraction may localize all species of chemical carcinogens and that this localization may be involved in the chemically induced malignant transformation of cells.

Original languageEnglish (US)
Pages (from-to)408-417
Number of pages10
JournalInternational Journal of Cancer
Volume20
Issue number3
StatePublished - 1977

Fingerprint

Inbred AKR Mouse
Methylnitronitrosoguanidine
Benzo(a)pyrene
Embryonic Structures
Cell Culture Techniques
Carcinogens
Radioactivity
Polycyclic Aromatic Hydrocarbons
Nitrosoguanidines
Alkylating Agents
Cell Nucleus
Centrifugation
Sucrose

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The binding of benzo(a)pyrene and N-methyl-N'-nitro-N-nitrosoguanidine to subnuclear fractions of AKR mouse embryo cells in culture. / Zytkovicz, T. H.; Moses, H. L.; Spelsberg, T. C.

In: International Journal of Cancer, Vol. 20, No. 3, 1977, p. 408-417.

Research output: Contribution to journalArticle

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