Mechanism of carcinogenesis induced by a veterinary antimicrobial drug, nitrofurazone, via oxidative DNA damage and cell proliferation

  • Cancer Lett. 2004 Nov 25;215(2):141-50. doi: 10.1016/j.canlet.2004.05.016.
Yusuke Hiraku  1 ,  Aki Sekine ,  Hiromi Nabeshi ,  Kaoru Midorikawa ,  Mariko Murata ,  Yoshito Kumagai ,  Shosuke Kawanishi
Affiliations
  • 1. Department of Environmental and Molecular Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
PMID: 15488632 DOI: 10.1016/j.canlet.2004.05.016
Abstract

Nitrofurazone, a veterinary antimicrobial drug, causes mammary and ovarian tumors in Animals. We investigated the mechanisms of carcinogenesis by nitrofurazone. Nitrofurazone significantly stimulated the proliferation of estrogen-dependent MCF-7 cells. Nitrofurazone caused Cu(II)-mediated damage to 32P-5'-end-labeled DNA fragments obtained from human genes only when Cytochrome P450 reductase was added. DNA damage was inhibited by catalase and bathocuproine. DNA damage was preferably induced at the 5'-ACG-3' sequence, a hotspot of the p53 gene. These findings suggest that nitrofurazone metabolites are involved in tumor initiation through oxidative DNA damage and nitrofurazone itself enhances cell proliferation, leading to promotion and/or progression in carcinogenesis.

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