Arsenic Enhancement of Skin Neoplasia by Chronic Stimulation of Growth-Promoting Cytokines

Details

• Personal Author:
  Bruccoleri A ; Chen GS ; Germolec DR ; Luster MI ; Simeonova PP ; Spalding J ; Yu HS
• Description:
  While numerous epideiological studies have shown that inorganic arsenicals cause skin cancers and hyperkeratoses in humans, there are currently no established mechanisms for their action or animal models. Previous studies in our laboratory using primary human keratinocyte cultures demonstrated that inorganic arsenite increased cell proliferation via the production of keratinocyte-derived growth factors. As recent reports suggest that overexpression of keratinocyte-derived growth factors. As recent reports suggest that overexpression of keratinocyte-derived growth factors may promote the formation of skin tumors, we hypothesized that similar events may be responsible for those associated with arsenic skin diseases. Thus, the influence of arsenic in humans with arsenic skin disease and on mouse skin tumor development in transgenic TG.AC mice which carry the v-Ha-ras oncogene was studied. Following low-dose application of TPA, a marked increase in the number of skin papillomas occurred in transgenic mice receiving arsenic in the drinking water as compared to control drinking water, while no papillomas developed in arsenic/TPA-treated wild-type FVB/N mice. Consistent with earlier in vivo findings, increases in GM-CSF and TGF mRNA transcripts were found in the epidermis of these mice at sites that appeared clinically normal within 10 weeks following arsenic treatment. Immunohistochemical staining localized GM-CSF and TGF overexpression to the hair follicles. Injection of neutralizing antibodies to GM-CSF following TPA application reduced the number of papillomas in TG.AC mice. Analysis of gene expression in samples of lesioned skin obtained from humans chronically exposed to arsenic via their drinking water also showed similar alterations in growth factor expression. These results suggest that arsenic enhances development of skin neopasias via the chronic stimulation of keratinocyte-derived growth factors and may be a unique example of a chemical carcinogen which acts as a co-promoter. [Description provided by NIOSH]
• Subjects:
  Animals Arsenic Epidemiology Inorganic Chemicals Laboratories Neoplasms Occupational Health Safety Skin Skin Diseases
• Keywords:
  Animal-studies Arsenic-compounds Arsenites Cancer In-vitro-studies In-vivo-studies Laboratory-animals Models Skin-cancer Skin-diseases
• Publisher:
  The Society for Environmental Geochemistry and Health
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  29
• NIOSHTIC Number:
  nn:20030402
• Citation:
  Third International Conference on Arsenic Exposure and Health Effects, July 12-15, 1998, San Diego, California. Syracuse NY: The Society for Environmental Geochemistry and Health, 1998 Jul; :29
• Contact Point Address:
  Dori R. Germolec, Ph. D., Environmental Immunology Laboratory, NIEHS, P.O. Box 12233, Research Triangle Park, NC 27709, USA
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2)
• Federal Fiscal Year:
  1998
• Peer Reviewed:
  False
• Source Full Name:
  Third International Conference on Arsenic Exposure and Health Effects, July 12-15, 1998, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:890781cc1fb8e811fccbeb6959518f972234a61ed09d3649ebd01a984e420fa1194a7b13db1be3281f2e66044421a873b905047e64db7fd254e840e6ad7a5482
• Download URL:
  https://stacks.cdc.gov/view/cdc/191040/cdc_191040_DS1.pdf
• File Type:
  [PDF - 155.71 KB ]