TNF-alpha is involved in activating DNA fragmentation in skeletal muscle

Br J Cancer. 2002 Mar 18;86(6):1012-6. doi: 10.1038/sj.bjc.6600167.


Intraperitoneal administration of 100 microg kg(-1) (body weight) of tumour necrosis factor-alpha to rats for 8 consecutive days resulted in a significant decrease in protein content, which was concomitant with a reduction in DNA content. Interestingly, the protein/DNA ratio was unchanged in the skeletal muscle of the tumour necrosis factor-alpha-treated animals as compared with the non-treated controls. Analysis of muscle DNA fragmentation clearly showed enhanced laddering in the skeletal muscle of tumour necrosis factor-alpha-treated animals, suggesting an apoptotic phenomenon. In a different set of experiments, mice bearing a cachexia-inducing tumour (the Lewis lung carcinoma) showed an increase in muscle DNA fragmentation (9.8-fold) as compared with their non-tumour-bearing control counterparts as previously described. When gene-deficient mice for tumour necrosis factor-alpha receptor protein I were inoculated with Lewis lung carcinoma, they were also affected by DNA fragmentation; however the increase was only 2.1-fold. These results suggest that tumour necrosis factor-alpha partly mediates DNA fragmentation during experimental cancer-associated cachexia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / physiology
  • Apoptosis*
  • Cachexia / etiology*
  • Carcinoma, Lewis Lung / blood
  • Carcinoma, Lewis Lung / complications
  • Carcinoma, Lewis Lung / pathology
  • DNA Fragmentation*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Receptors, Tumor Necrosis Factor / physiology
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / physiology*


  • Antigens, CD
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha