The Effects of Carcinogens and Irradiation on Cells and Tissues of the Eastern Red Spotted Newt (Notophthalmus viridescens)

Abstract

Newts, such as Notophthalmus viridescens, can regenerate many structures after amputation or injury and have also shown a refractory response to the formation of cancer in tissues that have regenerative capabilities. The mechanisms behind this latter ability have surprisingly not been studied. In the current study, N. viridescens were exposed to a variety of carcinogens in tissue that cannot regenerate with the intention of inducing tumour formation. After testing multiple carcinogens, multiple sites of injection, and two different modes of delivery, no tumours were generated. Consequently, in vitro assays were developed in order to better understand this ability of newt cells to evade transformation. Mouse and newt muscle cells were exposed to DNA damaging agents, such as irradiation and carcinogens, in culture and their response was monitored with respect to the DNA damage response proteins γ-H2AX, p53, and phospho-p53. These proteins are important as they help prevent mutations in the genome from being passed on to daughter cells and potentially generating cells that proliferate uncontrollably, a hallmark of cancer. Preliminary results suggest that after irradiation, γ-H2AX is present in newt cells for a considerably longer period of time in comparison to mouse cells. p53, as well as phospho-p53, appear to be present at a basal level before and after irradiation in newt cells, whereas mouse cells have a distinct increase upon damage and decrease upon repair. The carcinogen treatments also suggest that newt cells have basal levels of expression of these proteins prior to treatment. These studies suggest that newt cells may have a unique profile of these DNA damage response proteins and may be “primed” to repair any future damage. This is a good first step in understanding what is likely a very complicated explanation for newts’ refractory response to cancer formation.