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

Yusuke Hiraku, Aki Sekine, Hiromi Nabeshi, Kaoru Midorikawa, Mariko Murata, Yoshito Kumagai, Shosuke Kawanishi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)141-150
Number of pages10
JournalCancer Letters
Volume215
Issue number2
DOIs
Publication statusPublished - 25-11-2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Mechanism of carcinogenesis induced by a veterinary antimicrobial drug, nitrofurazone, via oxidative DNA damage and cell proliferation'. Together they form a unique fingerprint.

Cite this