Urinary bladder carcinogenesis by DNA reactive and non-reactive chemicals

Non-linearities and thresholds

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Chemicals can increase the risk of cancer by either directly damaging DNA (DNA reactive) or increasing cell proliferation. DNA reactive carcinogens involve activation to reactive metabolites, forming DNA adducts which are mutagenic. The presence of numerous cellular repair processes suggest that these could have a threshold. The issues involved are described for 2-acetylaminofluorene urinary bladder carcinogenicity. Chemicals that act by increasing cell proliferation involve either increased cell births or decreased cell deaths, leading to an accumulation of cells. Multiple mechanisms can produce these effects, most of which have threshold processes. Arsenicals appear to act by inducing cellular cytotoxicity with regenerative proliferation, induced by generation of reactive trivalent forms which interact with critical sulfhydryl groups in cells. A more definitive threshold response is illustrated for the formation of urinary solids, either calculi (melamine) amorphous calcium phosphate-containing precipitate (sodium saccharin) or crystalluria (PPAR g agonists). Increasing evidence strongly supports the concept of thresholds in carcinogenesis, not only for chemicals acting by increasing cell proliferation but also for those acting by DNA reactivity.

Original languageEnglish (US)
Pages (from-to)165-170
Number of pages6
JournalGenes and Environment
Volume34
Issue number4
DOIs
StatePublished - Dec 1 2012

Fingerprint

nonlinearity
Carcinogenesis
Urinary Bladder
DNA
Cell Proliferation
Arsenicals
2-Acetylaminofluorene
Saccharin
Peroxisome Proliferator-Activated Receptors
DNA Adducts
Calculi
Carcinogens
carcinogen
Cell Death
repair
Parturition
cancer
metabolite
calcium
phosphate

Keywords

  • Acetylaminofluorene
  • Arsenic
  • Melamine
  • PPARγ agonists
  • Saccharin
  • Urinary bladder

ASJC Scopus subject areas

  • Genetics
  • Environmental Science (miscellaneous)
  • Social Psychology

Cite this

Urinary bladder carcinogenesis by DNA reactive and non-reactive chemicals : Non-linearities and thresholds. / Cohen, Samuel Monroe.

In: Genes and Environment, Vol. 34, No. 4, 01.12.2012, p. 165-170.

Research output: Contribution to journalReview article

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