Inhibition of carcinogen-induced cellular transformation of human fibroblasts by drugs that interact with the poly(ADP-ribose) polymerase system. Initial evidence for the development of transformation resistance

FEBS Lett. 1985 Jan 7;179(2):332-6. doi: 10.1016/0014-5793(85)80546-9.

Abstract

Two types of interactions of 13 drugs with human fibroblasts were determined: I50 of nuclear poly(ADP-ribose) polymerase, as assayed with isolated nuclei in vitro, and the non-toxic concentration of drugs that prevented carcinogen-induced cell transformation of intact fibroblasts (RCF1). In general, RCF1 was much lower than I50, and one antitransformer did not inhibit the enzyme in vitro, indicating that low-affinity enzyme inhibitory sites appear to play no role in the mechanism of prevention of cell transformation. Two enzyme inhibitors, caffeine and 1-methylnicotinamide, exhibited no antitransforming activity. Benzamide when applied in population doubling 1 induced resistance to cell transformation in population doubling 6 by carcinogens added at this stage.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetamides / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Benzamides / pharmacology
  • Butylated Hydroxyanisole / pharmacology
  • Carcinogens*
  • Cell Transformation, Neoplastic / chemically induced
  • Cell Transformation, Neoplastic / drug effects*
  • Coumarins / pharmacology
  • Fibroblasts / enzymology*
  • Humans
  • NAD+ Nucleosidase / antagonists & inhibitors*
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Quercetin / pharmacology

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • Benzamides
  • Carcinogens
  • Coumarins
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Butylated Hydroxyanisole
  • Quercetin
  • coumarin
  • NAD+ Nucleosidase
  • hexamethylene bisacetamide