Molecular and cellular effects of ultraviolet light-induced genotoxicity

Helen R. Griffiths*, Pratibha Mistry, Karl E. Herbert, Joseph Lunec

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Exposure to the solar ultraviolet spectrum that penetrates the Earth's stratosphere (UVA and UVB) causes cellular DNA damage within skin cells. This damage is elicited directly through absorption of energy (UVB), and indirectly through intermediates such as sensitizer radicals and reactive oxygen species (UVA). DNA damage is detected as strand breaks or as base lesions, the most common lesions being 8-hydroxydeoxyguanosine (8OHdG) from UVA exposure and cyclobutane pyrimidine dimers from UVB exposure. The presence of these products in the genome may cause misreading and misreplication. Cells are protected by free radical scavengers that remove potentially mutagenic radical intermediates. In addition, the glutathione-S-transferase family can catalyze the removal of epoxides and peroxides. An extensive repair capacity exists for removing (1) strand breaks, (2) small base modifications (8OHdG), and (3) bulky lesions (cyclobutane pyrimidine dimers). UV also stimulates the cell to produce early response genes that activate a cascade of signaling molecules (e.g., protein kinases) and protective enzymes (e.g., haem oxygenase). The cell cycle is restricted via p53-dependent and -independent pathways to facilitate repair processes prior to replication and division. Failure to rescue the cell from replication block will ultimately lead to cell death, and apoptosis may be induced. The implications for UV-induced genotoxicity in disease are considered.

Original languageEnglish
Pages (from-to)189-237
Number of pages49
JournalCritical Reviews in Clinical Laboratory Sciences
Volume35
Issue number3
DOIs
Publication statusPublished - 21 Aug 1998

Bibliographical note

solar ultraviolet spectrum, UVA, UVB, cellular DNA damage, skin cell, absorption of energy, sensitizer radicals, reactive oxygen species, DNA damage, lesions, free radical scavengers, mutagenic radical intermediate, epoxide, peroxides, repair capacity, response gene, signaling molecule, protective enzymes, cell death, genotoxicity

Keywords

  • cancer
  • DNA damage
  • gene induction
  • repair
  • UVA
  • UVB

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