Potential role of environmental genotoxic agents in diabetes mellitus and neurodegenerative diseases

Décio L. Eizirik, Peter Spencer, Glen E. Kisby

Research output: Contribution to journalComment/debate

20 Scopus citations

Abstract

Epidemiological data suggest that environmental genotoxins are risk factors for some forms of diabetes mellitus and neurodegenerative diseases. The present commentary focuses on mechanisms involved in genotoxin-induced pancreatic β-cell and neuronal damage. These two cell types seem to share a similar vulnerability to different forms of DNA damage, and the long-term consequences of repeated genotoxic insults to post-mitotic neurons or slowly proliferating β-cells remain to be clarified. One intriguing possibility is that genotoxins could act as 'slow' toxins in these cells, triggering a cascade of cellular events, which culminates in progressive cell dysfunction and loss. Indeed, exposure to mutagenic nitroso agents such as streptozotocin and cycasin induces long-lasting damage to both β-cells and neurons. These data on cycasin, a toxin obtained from the cycad plant (Cycas spp.), are of special interest, since this agent may be implicated in both amyotrophic lateral sclerosis/Parkinson dementia complex and diabetes mellitus in the western Pacific area. Future studies are required to sort out the interactions between different genotoxic agents, viral infections, and cellular repair mechanisms on cellular survival and function. Moreover, further epidemiological studies are needed to clarify the role of N-nitrosoureas in diabetes mellitus and neurodegenerative diseases in populations with different genetic backgrounds. Answers to these questions may provide useful information on the pathogenesis of these devastating diseases, and open the possibility for their primary prevention.

Original languageEnglish (US)
Pages (from-to)1585-1591
Number of pages7
JournalBiochemical Pharmacology
Volume51
Issue number12
DOIs
StatePublished - Jun 28 1996

Keywords

  • DNA damage
  • DNA repair
  • N-nitrosamines
  • cycad
  • cycasin
  • diabetes mellitus
  • methylazoxymethanol
  • neurodegenerative diseases
  • pancreatic islets
  • streptozotocin

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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