Epidemiological studies have correlated arsenic exposure with cancer, skin diseases, and adverse developmental outcomes such as spontaneous abortions, neonatal mortality, low birth weight, and delays in the use of musculature. The current study used C2C12 mouse myoblast cells to examine whether low concentrations of arsenic could alter their differentiation into myotubes, indicating that arsenic can act as a developmental toxicant. Myoblast cells were exposed to 20 nM sodium arsenite, allowed to differentiate into myotubes, and expression of the muscle-specific transcription factor myogenin, along with the expression of tropomyosin, suppressor of cytokine signaling 3 (Socs3), prostaglandin I2 synthesis (Ptgis), and myocyte enhancer 2 (Mef2) were investigated using QPCR and immunofluorescence. Exposing C2C12 cells to 20nM sodium arsenite delayed the differentiation process, as evidenced by a significant reduction in the number of multinucleated myotubes, a decrease in myogenin mRNA expression, and a decrease in the total number of nuclei expressing myogenin protein. The expression of mRNA involved in myotube formation, such as Ptgis and Mef2 mRNA, was also significantly reduced by 1.6-fold and 4-fold during differentiation. This was confirmed by immunofluorescence for Mef2, which showed a 2.6-fold reduction in nuclear translocation. Changes in methylation patterns in the promoter region of myogenin (−473 to +90) were examined by methylation-specific PCR and bisulfite genomic sequencing. Hypermethylated CpGs were found at −236bp and −126bp, whereas hypomethylated CpGs were found at −207bp in arsenic exposed cells. This study indicates that 20 nM sodium arsenite can alter myoblast differentiation by reducing the expression of the transcription factors myogenin and Mef2c, which is likely due to changes in promoter methylation patterns. The delay is muscle differentiation may lead to developmental abnormalities.

Particles with a superparamagnetic cobalt inner core, silica outer core, and covalently bound homopolypeptide shell were investigated under thermal and magnetic stimuli. The homopolypeptide was poly(ε-carbobenzyloxy-L-lysine), PCBL, which is known to exhibit a thermoreversible coil ⇔ helix transition when dissolved as a pure polymer in m-cresol. Tethering to a core particle did not prevent PCBL from undergoing this conformational transition, as confirmed by dynamic light scattering and optical rotation, but the transition was broadened compared to that of the untethered polymer. The Co@SiO 2 -PCBL hybrid particles retained the superparamagnetic properties of the cobalt inner nougat. Indeed, some response remains even after aging for >5 years. The aged PCBL shell also preserved its responsiveness to temperature, although differences in the shape of the size vs temperature transition curve were observed compared to the freshly made particles. A reversible coil ⇔ helix transition for a particlebound polypeptide in a pure organic solvent is rare. In addition to providing a convenient tool for characterizing coil ⇔ helix transitions for surface-bound polypeptides without interference from pH or the strong ionic forces that dominate behavior in aqueous systems, the Co@SiO 2 -PCBL/m-cresol system may prove useful in studies of the effect of shell polymer conformation on colloid interactions. The stability of the magnetic core and polypeptide shell suggest a long shelf life for Co@SiO 2 -PCBL, which can, in principle, be deprotected to yield positively charged Co@SiO 2 -poly(L-lysine) particles for possible transfection or antimicrobial applications or chained magnetically to produce responsive poly(colloids).