Cancer Resistance in Amphibians

Abstract

While spontaneous tumours may occasionally develop in inbred and isogenic strains of Xenopus laevis, the South African clawed toad, they are extremely rare in natural and laboratory populations. Only two amphibian neoplasms, the renal adenocarcinoma of Rana pipiens and the lymphosarcoma of Xenopus laevis, have been extensively explored. Amphibians are resistant to the development of neo-plasia, even following exposure to “direct-acting” chemical carcinogens such as N-methyl- N-nitrosourea, that are highly lymphotoxic, thus diminishing immune reactivity. Regenerative capacity in adults, and a dramatic metamorphosis which remodels much of the larval body to produce the adult form, are unique to amphibian vertebrates, and the control mechanisms involved may protect against cancer. For example, naturally rising corticosteroid titres during metamorphosis will impair some T-cell functions, and the removal of T-regulatory (suppressor) functions inhibits the induction of altered-self tolerance. Altered-self tolerance is not as effectively induced in adult Xenopus laevis as in mammals, so cancer cells with new antigenicity are more likely be rejected in amphibians. Amphibian immunocytes tend to undergo apoptosis readily in vitro, and, unlike mammalian immunocytes, undergo apoptosis without entering the cell cycle. Cells not in the cell cycle that die from nuclear damage (apoptosis), will have no opportunity to express genetic instability leading to cell transformation. We suggest that all these factors, rather than any one of them, may reduce susceptibility to cancer in amphibians.

The free‐radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan

“…Certainly, there is an abundant amount of data indicating an association between elevated oxidative stress and increased risk of age‐related diseases like various cancers, cardiovascular disease and neurodegeneration. Yet one factor marking out organisms such as amphibians like the olm and the NMR is their extremely low rates of cancer, in spite of their unexceptional defences against oxidative stress 69. Consequently, the key to understanding the relationship of free radicals to degenerative disease and ultimately the process of ageing may not be obtained by trying to fathom whether animals have low or high rates of free‐radical production, or even whether they sustain high or low rates of oxidative damage, but rather how they mitigate, or not, translation of this damage into age‐related disease.…”

Cancer may be a pathway to cell survival under persistent hypoxia and elevated ROS: A model for solid‐cancer initiation and early development

“…A number of studies have been published, aiming to explain why some organisms such as amphibians, naked and blind mole rats do not develop cancers . The proposed mechanisms tend to be organism‐specific, such as alterable immune systems being used by amphibians, special abilities to resist ROS in blind mole rats and a capability in producing long hyaluronic acid polymers by naked mole rats . We suspect that there is something more fundamental than these proposals, some common characteristics shared by the basic metabolisms of these organisms, which are distinct from those cancer‐prone organisms.…”

Humane Anesthesia and Pain Management in Amphibian Limb Surgery of Rana pipiens

“…Adult Rana pipiens frogs are used as a model to investigate mechanisms of vertebrate organ regeneration (Smith 1967; Borgens et al 1977), anti-tumor ribonucleases (Ardelt et al 2007a,b; 2008; Lee and Raines 2008), zoological impacts of various pollutants (Shenoy et al 2009), oncogenesis (Outzen and Custer 1976; Outzen et al 1976; Ruben et al 2007), neuroplasticity (Constantine-Paton and Capranica 1976a,b; Maden 1981), and neurogenesis (Scalia et al 2009). This protocol provides a safe, reproducible, and humane technique to perform amputation surgery on adult amphibians, specifically Rana pipiens .…”