Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde (PPGBioSaúde), ULBRA, Canoas, RS, Brazil.
Laboratório de Estomatologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Sci Total Environ. 2014 Aug 15;490:679-85. doi: 10.1016/j.scitotenv.2014.05.047. Epub 2014 Jun 2.
Considering the limited number of studies on the biological effects on human health of cyanobacterial compounds that cause taste and odor, the present study assessed the cytotoxic and genotoxic potentials of 2-methylisoborneol (2-MIB) and geosmin (GEO) using the MTT assay and the in vitro comet and cytokinesis-block micronucleus (CBMN-Cyt) assays in human HepG2 cells. The toxicogenomics of genes responsive to DNA damage and metabolization by the exposure of cells to 2-MIB and GEO were also investigated. The results showed that concentrations of 2-MIB and GEO above 100 and 75 μg/mL, respectively, were cytotoxic to HepG2 cells. Doses of 2-MIB (12.5, 25, 50, 75 and 100 μg/mL) and GEO (12.5, 25, 50, and 75 μg/mL) were unable to induce neither DNA damage nor events associated with chromosomal instability. Similarly, no concentration of each compound induced increments in the expression of CDKN1A, GADD45α, MDM2 and TP53 DNA damage responsive genes as well as in CYP1A1 and CYP1A2 metabolizing genes. Although cytotoxicity was observed, concentrations that caused it are much higher than those expected to occur in aquatic environments. Thus, environmentally relevant concentrations of both compounds are not expected to exhibit cytotoxicity or genotoxicity to humans.
鉴于有关引起味道和气味的蓝藻化合物对人类健康的生物学影响的研究数量有限,本研究使用 MTT 测定法和体外彗星和胞质分裂阻断微核(CBMN-Cyt)测定法评估了 2-甲基异莰醇(2-MIB)和土臭素(GEO)的细胞毒性和遗传毒性潜能在人 HepG2 细胞中。还研究了细胞暴露于 2-MIB 和 GEO 时响应 DNA 损伤和代谢的基因的毒理基因组学。结果表明,浓度为 2-MIB 和 GEO 分别高于 100 和 75μg/mL 时对 HepG2 细胞具有细胞毒性。2-MIB(12.5、25、50、75 和 100μg/mL)和 GEO(12.5、25、50 和 75μg/mL)的剂量均不能诱导 DNA 损伤或与染色体不稳定性相关的事件。同样,每种化合物的浓度均未引起细胞周期蛋白依赖性激酶抑制剂 1A(CDKN1A)、GADD45α、MDM2 和 TP53 DNA 损伤反应基因以及细胞色素 P4501A1 和 CYP1A2 代谢基因的表达增加。尽管观察到细胞毒性,但引起该毒性的浓度远高于预期在水生环境中出现的浓度。因此,预计两种化合物的环境相关浓度不会对人类表现出细胞毒性或遗传毒性。