Endocrine disruptive effects of cadmium on steroidogenesis: Human adrenocortical carcinoma cell line NCI-H295R as a cellular model for reproductive toxicity testing

• Published in: Journal of environmental science and health. Part A, Toxic/hazardous substances & environmental engineering Toxic/hazardous substances & environmental engineering, 2015-03, Vol.50 (4), p.348-356
• Main Authors: Knazicka, Zuzana, Forgacs, Zsolt, Lukacova, Jana, Roychoudhury, Shubhadeep, Massanyi, Peter, Lukac, Norbert
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Neoplasms - metabolism; Adrenal Cortex Neoplasms - pathology; Adrenocortical Carcinoma - metabolism; Adrenocortical Carcinoma - pathology; Assaying; Biosynthesis; Biotechnology; Cadmium; Cadmium chloride; Cadmium Chloride - toxicity; Cell Line, Tumor - drug effects; Cell Survival - drug effects; cell viability; Cellular; Cytotoxicity; Dose-Response Relationship, Drug; endocrine disruption; Endocrine Disruptors - toxicity; Enzyme-Linked Immunosorbent Assay; Enzymes; Estradiol - biosynthesis; Human; Humans; Immunoassay; Mitochondria; NCI-H295R cell line steroid hormones; Progesterone - biosynthesis; Steroids; Testosterone; Testosterone - biosynthesis; Toxicity Tests - methods; Viability
• ISSN: 1093-4529; 1532-4117
• DOI: 10.1080/10934529.2015.987520

Cadmium (Cd) is a known endocrine disruptor with the ability to affect the production of hormones involved in the regulation of reproductive processes. In this study human adrenocortical carcinoma cell line NCI-H295R was used as an in vitro biological model to study the effect of cadmium (CdCl 2 ) on steroidogenesis. The cell cultures were exposed to different concentrations of CdCl 2 (1.90, 3.90, 7.80, 15.60, 31.20 and 62.50 μM) and compared to control (medium without CdCl 2 ). Cell viability was measured by the metabolic activity (MTT) assay for estimation of mitochondria structural integrity. Quantification of sexual steroid production directly from aliquots of the medium was performed by enzyme linked immunosorbent assay (ELISA). Following 48 h culture of the cells in the presence of CdCl 2 a concentration-dependent depletion in progesterone production was observed at the lower concentrations of CdCl 2 . The lowest amount of progesterone was significantly detected in groups with the higher doses (≥ 31.20 μM) of CdCl 2 , which elicited significant (P < 0.01) cytotoxic action, too. Cadmium decreased testosterone release in the whole applied range even at the lower concentration of CdCl 2 . The release of 17β-estradiol decreased as well, but the decline was less pronounced compared to decrease of progesterone and testosterone. The cytotoxic effect was significantly (P < 0.01) detected at all concentrations of CdCl 2 (1.90-62.50 μM) used in the study. However, the cell viability remained relatively high (>75%) up to 7.80 μM of CdCl 2 and significantly (P < 0.01) decreased at 15.60 μM and higher concentrations of CdCl 2 . These results suggest that cadmium has endocrine disruptive effects on sexual steroid synthesis even at very low concentrations.