Molecular effects of 1-naphthyl-methylcarbamate and solar radiation exposures on human melanocytes.

Autor: Ferrucio B; Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil, 05508-000. Electronic address: biferrucio@usp.br., Tiago M; Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil, 05508-000. Electronic address: manoela.santos@usp.br., Fannin RD; NIEHS Molecular Genomics Core Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA, 27709. Electronic address: fannin@niehs.nih.gov., Liu L; NIEHS Molecular Genomics Core Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA, 27709. Electronic address: liuliw@niehs.nih.gov., Gerrish K; NIEHS Molecular Genomics Core Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA, 27709. Electronic address: gerrish@niehs.nih.gov., Maria-Engler SS; Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil, 05508-000. Electronic address: silvya@usp.br., Paules RS; NIEHS Molecular Genomics Core Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA, 27709. Electronic address: paules@niehs.nih.gov., Barros SBM; Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil, 05508-000. Electronic address: smbarros@usp.br.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2017 Feb; Vol. 38, pp. 67-76. Date of Electronic Publication: 2016 Nov 06.
DOI: 10.1016/j.tiv.2016.11.005
Abstrakt: Carbaryl (1-naphthyl-methylcarbamate), a broad-spectrum insecticide, has recently been associated with the development of cutaneous melanoma in an epidemiological cohort study with U.S. farm workers also exposed to ultraviolet radiation, the main etiologic factor for skin carcinogenesis. We hypothesized that carbaryl exposure may increase deleterious effects of UV solar radiation on skin melanocytes. This study aimed to characterize human melanocytes after individual or combined exposure to carbaryl (100μM) and solar radiation (375mJ/cm 2 ). In a microarray analysis, carbaryl, but not solar radiation, induced an oxidative stress response, evidenced by the upregulation of antioxidant genes, such as Hemeoxygenase-1 (HMOX1), and downregulation of Microphtalmia-associated Transcription Factor (MITF), the main regulator of melanocytic activity; results were confirmed by qRT-PCR. Carbaryl and solar radiation induced a gene response suggestive of DNA damage and cell cycle alteration. The expression of CDKN1A, BRCA1/2 and MDM2 genes was notably more intense in the combined treatment group, in a synergistic manner. Flow cytometry assays demonstrated S-phase cell cycle arrest, reduced apoptosis levels and faster induction of cyclobutane pyrimidine dimers (CPD) lesions in carbaryl treated groups. Our data suggests that carbaryl is genotoxic to human melanocytes, especially when associated with solar radiation.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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