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Carcinogenesis Advance Access published online on June 17, 2004
Carcinogenesis, doi:10.1093/carcin/bgh218
© 2004 by Oxford University Press
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Received March 26, 2004
Revised May 27, 2004
Accepted June 10, 2004

CANCER BIOLOGY

Inducible NO synthase inhibits the growth of free tumor cells, but enhances the growth of solid tumors

Manabu Nishikawa 1*, BaoJun Chang 1, Masayasu Inoue 1

1 Department of Biochemistry, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; Department of Molecular Pathology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan

* To whom correspondence should be addressed. E-mail: nishikawa{at}med.osaka-cu.ac.jp.


  Abstract

To elucidate the role of nitric oxide (NO) in tumor cell growth in vivo, dynamic aspects of the growth of Ehrlich ascites tumor cells (EATCs) were studied in wild type (WT) mice and in an inducible strain of NO synthase (iNOS)-deficient (iNOS-/-) mice. Kinetic analysis showed that the rate of free tumor cell growth in the peritoneal cavity was significantly higher in the iNOS-/- mice than in the WT mice. In contrast, EATCs inoculated subcutaneously rapidly grew and formed a solid tumor in WT mice, but failed to grow in iNOS-/- mice. These results clearly indicate that NO generated by iNOS predominantly inhibits the growth of tumor cells in their free form, but enhances the growth of solid tumors.

Keywords: tumor, growth, NO, iNOS, mitochondria
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