The reactions to carcinogens in the axolotl (Ambystoma mexicanum) in relation to the ‘regeneration field control’ hypothesis

About 200 axolotls, between 5 and 21 months old, were treated in the body wall with carcinogens or control substances, by subcutaneous or intradermal injection, or by sub-cutaneous implantation. In response to an injection of dibenzanthracene in olive oil an initial reaction appeared within 13 days. This consisted of an epidermal proliferation and a subcutaneous infiltration of macrophages. The epidermis returned to normal after several weeks, but the subcutaneous response took 6 months to disappear. The initial reaction appeared to be, at least partially, a wound healing response; its regression could not have been due to regeneration field control as it occurred in the posterior body region. Following the disappearance of the initial reaction a secondary reaction of papilloma-like outgrowths arose between 7 and 20 months after injection. Of the axolotls surviving for a sufficient length of time, outgrowths arose in 14 out of 54 animals injected with dibenz-anthracene and in 18 out of 57 sites injected with methylcholanthrene. These outgrowths had some features in common with the papillomata of mice, but none have yet progressed to carcinomata. In a group of axolotls injected in three different regions the frequency of out-growths varied according to the sites; however, this was thought to be due to differences in the difficulty of injecting the three regions. Two tumours, a sarcoma and a hepatoma, arose in the course of these experiments, 3 and 2 years respectively after carcinogen treatment. From this it is suggested tentatively that tumour induction by polycyclic hydrocarbons in the axolotl may require a long latent period and involve a low tumour incidence; however, it is possible that at least one of the tumours was not induced by the treatment.