We study the metastability, internal frequencies, activation mechanism, energy transfer, and the collective base-flipping in a mesoscopic DNA via resonance with specific electric fields. Our new mesoscopic DNA model takes into account not only the issues of helicity and the coupling of an electric field with the base dipole moments, but also includes environmental effects, such as fluid viscosity and thermal noise. Also, all the parameter values are chosen to best represent the typical values for the opening and closing dynamics of a DNA. Our study shows that while the mesoscopic DNA is metastable and robust to environmental effects, it is vulnerable to certain frequencies that could be targeted by specific THz fields for triggering its collective base-flipping dynamics and causing large amplitude separation of base pairs. Based on applying the Freidlin-Wentzell method of stochastic averaging and the newly developed theory of resonant enhancement to our mesoscopic DNA model, our semi-analytic estimates show that the required fields should be THz fields with frequencies around 0.28 THz and with amplitudes in the order of 450 kV/cm. These estimates compare well with the experimental data of Titova et al., which have demonstrated that they could affect the function of DNA in human skin tissues by THz pulses with frequencies around 0.5 THz and with a peak electric field at 220 kV/cm. Moreover, our estimates also conform to a number of other experimental results, which appeared in the last couple years.