© 1987 Oxford University Press
research-article |
Hydrogen peroxide formation and DNA base modification by tumor promoter-activated polymorphonuclear leukocytes
1Department of Environmental Medicine 550 First Avenue, New York, NY 10016, USA
2Department of Pathology, New York University Medical Center 550 First Avenue, New York, NY 10016, USA
3whom reprint requests should be sent
This report shows that generation of hydrogen peroxide (H2O2) by human polymorphonuclear leukocytes (PMNs) activated wtih tumor promoters of varying potency as first and second stage promoters correlates well with activities of these promoters in vivo. Those tested were 12-O-tetradeca-noylphorbol-13-acetate (TPA), a complete promoter, 12-0-retinoylphorbol-13-acetate (RPA), a synthetic TPA derivative almost devoid of first stage activity in some strains of mice, and mezerein (Mez), a potent second stage and much weaker first stage promoter. Mez-stimulated PMNs produced up to four times less H2O2 whereas RPA-stimulated PMNs pro-duced up to 10 times less H2O2 than TPA-activated cells when used at concentrations between 0.5 and 15 nM to activate 7.5–8.5 x 10 PMNs/ml. Phorbol, a non-promoter, was totally inactive in this assay. Furthermore, the tumor pro-moter-activated PMNs caused formation of 5-hydroxymethyl-2'-deoxyuridine (HMdU) and thymidine glycol (dTG) in DNA co-incubated with those cells. The amounts of modified thy-midines formed, particularly of HMdU, correlated well with first stage tumor promoting efficacy and with the amount of H2O2 that was generated by promoter activated PMNs. In comparison with TPA, Mez-or RPA-stimulated PMNs in-duced formation of 25 or 70% less H2O2 and 30 or 75% less HMdU, respectively, under conditions favoring HMdU for-mation. Thus, formation of either H2O2 by tumor promoter-stimulated phagocytes or HMdU in DNA exposed to those activated cells may serve as a measure of potency as a first stage tumor promoter. Formation of modified bases such as HMdU in DNA might constitute the genetic change imparted by the first stage tumor promoters.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. M. Knaapen, N. Gungor, R. P. F. Schins, P. J. A. Borm, and F. J. Van Schooten Neutrophils and respiratory tract DNA damage and mutagenesis: a review Mutagenesis, July 1, 2006; 21(4): 225 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.W. Boots, G.R.M.M. Haenen, and A. Bast Oxidant metabolism in chronic obstructive pulmonary disease Eur. Respir. J., November 2, 2003; 22(46_suppl): 14s - 27s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Li, J. Eckard, R. Shah, C. Malluck, and K. Frenkel Interleukin-1{alpha} Up-Regulation in Vivo by a Potent Carcinogen 7,12-Dimethylbenz(a)anthracene (DMBA) and Control of DMBA-induced Inflammatory Responses Cancer Res., January 1, 2002; 62(2): 417 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Chu, N. E. Ward, and C. A. O'Brian Potent inactivation of representative members of each PKC isozyme subfamily and PKD via S-thiolation by the tumor-promotion/progression antagonist glutathione but not by its precursor cysteine Carcinogenesis, August 1, 2001; 22(8): 1221 - 1229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhao, M. Lahiri-Chatterjee, Y. Sharma, and R. Agarwal Inhibitory effect of a flavonoid antioxidant silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin Carcinogenesis, April 1, 2000; 21(4): 811 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Gundimeda, Z.-H. Chen, and R. Gopalakrishna Tamoxifen Modulates Protein Kinase C via Oxidative Stress in Estrogen Receptor-negative Breast Cancer Cells J. Biol. Chem., June 7, 1996; 271(23): 13504 - 13514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Perera Carcinogens and human health: Part 1 Science, December 21, 1990; 250(4988): 1644 - 1646. [PDF]
|
|
|
|
|
|
B. Ames, R Magaw, and L. Gold Ranking possible carcinogenic hazards Science, April 17, 1987; 236(4799): 271 - 280. [Abstract] [PDF]
|
|
|
|
|
|
J. S. Liou, C.-Y. Chen, J. S. Chen, and D. V. Faller Oncogenic Ras Mediates Apoptosis in Response to Protein Kinase C Inhibition through the Generation of Reactive Oxygen Species J. Biol. Chem., December 8, 2000; 275(50): 39001 - 39011. [Abstract] [Full Text] [PDF]
|
|