Effects and Interactions of Low Doses of Arsenic and UVB on Keratinocyte Apoptosis
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- 作者：Chih-Hung Lee ; Chia-Li Yu ; Wei-Ting Liao ; Ying-Hsien Kao ; Chee-Yin Chai ; Gwo-Shing Chen ; and Hsin-Su Yu
- 刊名：Chemical Research in Toxicology
- 出版年：2004
- 出版时间：September 2004
- 年：2004
- 卷：17
- 期：9
- 页码：1199 - 1205
- 全文大小：147K
- 年卷期：v.17,no.9(September 2004)
- ISSN：1520-5010
文摘
Although arsenic and ultraviolet light B (UVB) are both causes for skin cancers, lesions ofarsenic-induced Bowen's disease are often confined to sun-protected skin. UVB may play amodulatory role in skin carcinogenesis by arsenic. The purpose of this study was to evaluatethe effects and interactions of arsenic and UVB on cell cycle progression and apoptosis. Culturedhuman keratinocytes were treated with sodium arsenite (1 
M) and/or UVB (50 mJ/cm2)irradiation in different combinations: (i) arsenic alone, (ii) UVB alone, (iii) arsenic followedby UVB (As-UVB), and (iv) UVB followed by arsenic (UVB-As) treatments. Cell cycle analysisand BrdU pulsing revealed S phase arrest in all treatment groups and growth arrest in As-UVB and UVB-As groups. The terminal deoxynucleotidyl transferase-mediated deoxyuridinenick-end labeling assay showed a higher apoptosis rate in the UVB-As group as compared tothat of the As-UVB and UVB groups. UVB irradiation significantly decreased Bcl-2 expression.In either the As-UVB or the UVB-As group, the expression of Bcl-2 was further suppressedas compared to the UVB group. The caspase-3, -8, and -9 relative activities were all increasedin the UVB group; however, arsenic significantly enhanced caspase-8 and -3 relative activitiesin UVB-irradiated keratinocytes (the UVB-As group). Pretreatment with the caspase inhibitor(s) rescued the keratinocytes viability to different degrees with the least in the UVB-As group.Our findings revealed that arsenic enhances UVB-induced keratinocyte apoptosis via suppression of Bcl-2 expression and stimulation of caspase-8 activity. Combined UVB and arsenictreatment resulted in the antiproliferative and proapoptotic effects in keratinocytes. Our resultsprovide the explanation for the rare occurrences of arsenical cancers in the sun-exposed skinand the potential therapeutic role of UVB in arsenic-induced Bowen's disease.
M) and/or UVB (50 mJ/cm2)irradiation in different combinations: (i) arsenic alone, (ii) UVB alone, (iii) arsenic followedby UVB (As-UVB), and (iv) UVB followed by arsenic (UVB-As) treatments. Cell cycle analysisand BrdU pulsing revealed S phase arrest in all treatment groups and growth arrest in As-UVB and UVB-As groups. The terminal deoxynucleotidyl transferase-mediated deoxyuridinenick-end labeling assay showed a higher apoptosis rate in the UVB-As group as compared tothat of the As-UVB and UVB groups. UVB irradiation significantly decreased Bcl-2 expression.In either the As-UVB or the UVB-As group, the expression of Bcl-2 was further suppressedas compared to the UVB group. The caspase-3, -8, and -9 relative activities were all increasedin the UVB group; however, arsenic significantly enhanced caspase-8 and -3 relative activitiesin UVB-irradiated keratinocytes (the UVB-As group). Pretreatment with the caspase inhibitor(s) rescued the keratinocytes viability to different degrees with the least in the UVB-As group.Our findings revealed that arsenic enhances UVB-induced keratinocyte apoptosis via suppression of Bcl-2 expression and stimulation of caspase-8 activity. Combined UVB and arsenictreatment resulted in the antiproliferative and proapoptotic effects in keratinocytes. Our resultsprovide the explanation for the rare occurrences of arsenical cancers in the sun-exposed skinand the potential therapeutic role of UVB in arsenic-induced Bowen's disease.