Site‐specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening

Oikawa, Shinji; Kawanishi, Shosuke

doi:10.1016/s0014-5793(99)00748-6

Cited by 365 publications

(283 citation statements)

References 46 publications

Supporting

Mentioning

268

Contrasting

Unclassified

Order By: Relevance

“…ROS, as induced by UVA radiation, are known to cause breaks in G-rich sequences (von Zglinicki et al, 2000). Actually, it was shown that telomeric DNA was 5 to 10-fold more assailable than nontelomeric DNA (Oikawa and Kawanishi, 1999). Thus, telomeres should be optimal substrates for UVA radiation.…”

Section: Discussionmentioning

confidence: 99%

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes

et al. 2008

View full text Add to dashboard Cite

The role of UVA-radiation-the major fraction in sunlight-in human skin carcinogenesis is still elusive. We here report that different UVA exposure regime (4 Â 5 J/cm 2 per week or 1 Â 20 J/cm 2 per week) caused tumorigenic conversion (tumors in nude mice) of the HaCaT skin keratinocytes. While tumorigenicity was not associated with general telomere shortening, we found new chromosomal changes characteristic for each recultivated tumor. Since this suggested a nontelomere-dependent relationship between UVA irradiation and chromosomal aberrations, we investigated for alternate mechanisms of UVA-dependent genomic instability. Using the alkaline and neutral comet assay as well as c-H2AX foci formation on irradiated HaCaT cells (20-60 J/cm 2 ), we show a dosedependent and long lasting induction of DNA single and double (ds) strand breaks. Extending this to normal human skin keratinocytes, we demonstrate a comparable damage response and, additionally, a significant induction and maintenance of micronuclei (MN) with more acentric fragments (indicative of ds breaks) than entire chromosomes particularly 5 days post irradiation. Thus, physiologically relevant UVA doses cause long-lasting DNA strand breaks, a prerequisite for chromosomal aberration that most likely contribute to tumorigenic conversion of the HaCaT cells. Since normal keratinocytes responded similarly, UVA may likewise contribute to the complex karyotype characteristic for human skin carcinomas.

show abstract

Section: Discussionmentioning

confidence: 99%

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The GGG-specific DNA damage by oxidative stress in telomere sequence may play an important role in increasing of the rate of telomere shortening (42,51). UVA radiation plus riboflavin induced 8-oxodG formation specifically at the GGG sequence in telomere through electron transfer.…”

Section: Resultsmentioning

confidence: 99%

Sequence-specific DNA damage by reactive oxygen species: Implications for carcinogenesis and aging

Oikawa

2005

Environ Health Prev Med

Self Cite

View full text Add to dashboard Cite

Reactive oxygen species (ROS) generated by environmental chemicals can cause sequence-specific DNA damage, which may lead to carcinogenesis and aging. We investigated the mechanism of DNA damage by environmental chemicals (catechol, propyl gallate and bisphenol-A), homocysteine and UVA radiation using human cultured cell lines and 32 P-labeled DNA fragments. Carcinogenic catechol induced piperidine-labile sites frequently at thymine residues in the presence of Cu(II) and NADH. Furthermore, catechol increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60, but not in HP100, a hydrogen peroxide (H 2 O 2 )-resistant cell line derived from HL-60. Thus, it is concluded that oxidative DNA damage through generation of H 2 O 2 plays an important role in the carcinogenic process of catechol. In addition, an environmental factor, bisphenol-A, and a dietary factor, propyl gallate, also induced sequence-specific DNA damage via ROS generation.UVA, as well as UVB, contributes to photoaging. In humans, telomere shortening is believed to be associated with cell senescence. In this study, we investigated the shortening rate of telomeres in human WI-38 fibroblasts exposed to UVA irradiation. The telomere length (as measured by terminal restriction fragment length) in WI-38 fibroblasts irradiated with UVA decreased with increasing the irradiation dose. UVA irradiation with riboflavin caused damage specifically at the GGG sequence in the DNA fragments containing telomere sequence (TTAGGG) 4 . We concluded that the GGG-specific damage in telomere sequence induced by UVA irradiation participates in the increase of the telomere shortening rate.In this report, we show our experimental results and discuss the mechanisms of sequence-specific DNA damage in relation to carcinogenesis and aging.

show abstract

“…One of the mechanisms is a pathway mediated by several biochemical factors like oxygen radicals (14). The structure of chromosomal ends consists of single-stranded overhangs with GGG-triplet repeat sequences, which is a major target of reactive oxygen species (17). Therefore, the telomere length of human tissues may also be influenced by the extent of oxidative stress, and the shortening of telomere length might be prevented by antioxidant agents (18).…”

Section: Discussionmentioning

confidence: 99%

Telomere Shortening of Peripheral Blood Mononuclear Cells in Coronary Disease Patients with Metabolic Disorders.

et al. 2003

View full text Add to dashboard Cite

Objective Telomere shortening is correlated with cell turnover and aging, but it has been recently suggested to occur not only by aging but by several biochemical fac- Results The results demonstrated that HCand/or DM patients with coronary diseases have significantly shorter telomere length than healthy controls (p=0.0014). Conclusion Telomere shortening may be involved in the mechanismsthat promote coronary diseases under some circumstances of metabolic disorders. (Internal Medicine 42: 150-153, 2003)

show abstract

Site‐specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening

Cited by 365 publications

References 46 publications

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes

Sequence-specific DNA damage by reactive oxygen species: Implications for carcinogenesis and aging

Telomere Shortening of Peripheral Blood Mononuclear Cells in Coronary Disease Patients with Metabolic Disorders.

Contact Info

Product

Resources

About