PFOI stimulates the motility of T24 bladder cancer cells: Possible involvement and activation of lncRNA malat1.

Perfluorinated iodine alkanes (PFIs) can serve as an important raw materials for the synthesis of various perfluorinated chemical products through telomerization reaction. The estrogenic effects of PFIs have been reported previously by some in vitro and in vivo screening assays. To explore the potential epigenetic toxicity of PFIs, activation of lncRNAs was screened, and the cell motility changes induced by perfluorooctyl iodide (PFOI) were analyzed in this study. High metastatic bladder cell line (T24) was used to investigate the cellular migration function affected by PFOI. PFOI exposure significantly induced the upregulation of lncRNA anril, thorlnc, hotairm1, meg3, and malat1. The migration and invasion of T24 cells were also enhanced upon PFOI exposure. The transcription level of matrix metalloenzyme genes, epidermal growth factors, cytoskeleton genes, and the upstream factors involved in cell motility pathways were examined to illustrate possible mechanisms. Additionally, the basic role of malat1 in cellular motility was investigated by lncRNA knockdown and migration assays. The knockdown of malat1 inhibited the cellular motility induced by PFOI. The levels of MMP-2/-9 genes were also down-regulated by the treatment of si-malat1. Overall, the perturbation of cytoskeleton genes (E-cadherin/N-cadherin) may account for the impact on the motility of T24 cells. Our studies indicate that perfluorinated chemicals might regulate the lncRNAs, thus promoting the metastasis of the tumor cells.

Evaluation of hypopigmentation in embryonic zebrafish induced by emerging disinfection byproduct, 3, 5-di-I-tyrosylalanine.

Halogenated dipeptides, 3, 5-di-I-tyrosylalanine (DIYA), have been identified as novel disinfection byproducts (DBPs), following chloramination of authentic water. However, little is known about their toxicity. Zebrafish embryos were used to assess the toxicity of novel iodinated DBPs (I-DBPs). Although DIYA did not exhibit high acute toxicity to embryonic zebrafish (LC50 > 2 mM), it significantly inhibited pigmentation of melanophores and xanthophores on head, trunk and tail at 500 µM as determined by photographic analysis. Whereas N-phenylthiourea (PTU) as a pigment inhibitor did not inhibit development of yellow pigments. Colorimetric detection of melanin further confirmed these results. Quantitative real time polymerase chain reaction (qRT-PCR) measurements indicated that genes (dct, slc24a5, tyr, tyrp1a, tyrp1b, silva) associated with the melanogenesis pathway were dramatically down-regulated following exposure to 500 µM DIYA. In addition, enzymatic activity of tyrosinase (TYR) decreased, also demonstrating that the underlying mechanism of hypopigmentation was attributed to the disruption of melanogenesis pathway. Transcription levels of xanthophore genes (gch2, bnc2, csf1a, csf1b, pax7a and pax7b) were also monitored by qRT-PCR assay. DIYA exposure up-regulated expression of gch2 and bnc2, but not csf1 and pax7. Tested DIYA analogues, brominated tyrosine was unlikely to inhibit pigmentation, indicating that the iodine substitution and dipeptides structure are of important structural feature for the inhibition of pigmentation. In this study, we observed that DIYA inhibited melanogenesis related genes, which might contribute to pigmentation defects. Moreover, as an emerging I-DBPs, the developmental toxicity of aromatic dipeptides should be further studied.