UV-A induces persistent genomic instability in human keratinocytes through an oxidative stress mechanism

Free Radic Biol Med. 2002 Mar 1;32(5):474-80. doi: 10.1016/s0891-5849(01)00829-2.

Abstract

Ultraviolet-A (UV-A, 320 to 400 nm) radiation comprises 95% of the solar ultraviolet radiation (UVR) reaching the earth's surface. It has been associated experimentally and epidemiologically with malignant melanoma. In this study we investigated whether UV-A radiation can induce a persistent, heritable hypermutability in mammalian cells similar to that observed following ionising radiation (IR). Using the immortalized human skin keratinocyte cell line HaCaT we found that UV-A radiation does lead to a continuing reduction in plating efficiency, an increased "spontaneous" mutant fraction, and an increase in micronucleus formation up to 21 d after initial exposure. Reversal of these effects using catalase may indicate a role for hydrogen peroxide in this phenomenon. These results add to the significance of UV-A radiation as a risk factor in skin carcinogenesis.

Publication types

  • Comparative Study

MeSH terms

  • Catalase / metabolism
  • Cell Division
  • Cells, Cultured / radiation effects*
  • Colony-Forming Units Assay
  • Comet Assay
  • DNA Damage / drug effects
  • DNA Damage / radiation effects*
  • Dose-Response Relationship, Radiation
  • Glutathione Transferase / metabolism
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects*
  • Micronuclei, Chromosome-Defective / drug effects
  • Micronuclei, Chromosome-Defective / genetics*
  • Micronuclei, Chromosome-Defective / radiation effects*
  • Mutation / radiation effects
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism
  • Skin Neoplasms / genetics*
  • Superoxide Dismutase / metabolism
  • Ultraviolet Rays

Substances

  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • Catalase
  • Superoxide Dismutase
  • Glutathione Transferase