Molecular effects of 1-naphthyl-methylcarbamate and solar radiation exposures on human melanocytes. (February 2017)

• Record Type: Journal Article
• Authors: Ferrucio, Bianca; Tiago, Manoela; Fannin, Richard D.; Liu, Liwen; Gerrish, Kevin; Maria-Engler, Silvya Stuchi; Paules, Richard S.; Barros, Silvia Berlanga de Moraes
• Is Part Of: Toxicology in vitro. Volume 38(2017)
• Page Start: 67
• Page End: 76
• Publication Date: 2017-02
• Subjects: Carbaryl -- 1-naphthyl-methylcarbamate -- Melanocytes -- Microarray -- Solar radiation -- Melanomagenesis; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2016.11.005
• Languages: English
• ISSNs: 0887-2333

Abstract

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 μM) 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 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. Graphical abstract: Highlights: Carbaryl exposure may increase solar radiation deleterious effects on melanocytes. Carbaryl, but not solar radiation, induced an oxidative stress response. Carbaryl treatment upregulated the antioxidant gene HMOX1 and inhibited MITF . Combined treatment group induced synergistic DNA damage and cell cycle alteration. Data suggests carbaryl genotoxicity to melanocytes when associated with solar UV.