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

Author(s)

Ferrucio, Bianca ; Tiago, Manoela ; Fannin, Richard D. ; Liu, Liwen ; Gerrish, Kevin ; Maria-Engler, Silvya Stuchi ; Paules, Richard S. ; de Moraes Barros, Silvia Berlanga

• Document type: Journal article
• Source: TOXICOLOGY IN VITRO; v. 38, p. 67-76, FEB 2017.
• Web of Science Citations: 1

Abstract

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 (100 mu M) and solar radiation (375 mJ/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 CDKNIA, 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. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 11/12616-0 - Carbaryl influence on the effects of UV radiation in human melanocytes in culture
• Grantee: Silvia Berlanga de Moraes Barros
• Support type: Regular Research Grants
• FAPESP's process: 10/17891-7 - Evaluation of the carbaryl influence on the effects of UV radiation in human melanocytes culture
• Grantee: Bianca Ferrucio
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/23621-8 - Gene expression profiling of human melanocyte cells after exposure to carbaryl and UV radiation
• Grantee: Bianca Ferrucio
• Support type: Scholarships abroad - Research Internship - Doctorate