The effect of methotrexate (amethopterin) on wound healing: an experimental study

Abstract

THE value of cytotoxic agents in the treatment of cancer is now established, and the comparative place of the many available agents in different tumours is now becoming clear (Davies 1964). In this respect, methotrexate is accepted as the drug of choice for epithelioma of the head and neck, although it is less clear how and when it should be employed.Given intra-arterially and used as the sole agent in regional infusion therapy, about 10% of tumours are cured and nearly 50 % show partial regression (Burn, 1964;Johnston, 1964). Although these results are full of promise they are nonetheless disappointing. Some form of adjuvant therapy has therefore been recommended. Philip (1964) has shown that the cure rate can be improved when methotrexate is combined with radiotherapy, and Routledge (1964) has used it before surgical excision of a tumour. Although improved survival figures can be shown by combined techniques, they are small in relation to the numbers who show local recurrence of their tumours. A new method of treatment, in which methotrexate was infused intra-arterially before and after surgical excision of the tumour, seemed worthy of trial. Before starting such a trial we wished to study the effect of methotrexate on wound healing experimentally. MATERIALSWe chose white Norwegian (" Wistar ") rats because they had been used in the study of wound healing many times before, and the findings appear to be comparable with those in man. All were young (4-6 weeks) females. METHODSFour standard wounds were made on the backs of a group of rats of similar weight and the animals allocated at random to one form of treatment. Adequate controls were used in every experiment. The tensile strength of the wounds was measured 3, 5 and 7 days after wounding, using a Sandblom tensiometer (Calnan and Fry, 1963). The measurements were made without reference to treatment, and the data examined by an analysis of variance. The methotrexate, or other drug, was freshly made up and given intraperitoneally in 1 c.c. volumes each day. The rats were housed in separate cages at room temperature and fed on a pellet diet (Dixon's No. 7) with water ad libitum.Six experiments were performed.

Effects of Cyclophosphamide on Mechanical Properties of Bone and Skin in Rats

“…As far as wound tensile strength is concerned, the present results are in agreement with the findings of DesPrez & Kiehn (1960). Also the observations of Calnan & Davies (1965) agree with those of the present study as they found no significant effect on wound tensile strength after a total dose of 35 mg/kg spread over 5 days. The effect of elevated dose levels on the tensile strength of incisional wounds are in agreement with the results of Cohen et al (1975).…”

The neutrophilic leukocyte in wound repair

“…The experiments of Selye (10) (24,25). (26,27). On the other hand, the use of antineutrophil serum provided a specific method for depleting circulating neutrophils with as little systemic trauma as possible (15).…”

Influence of Cis-Platinum on Healing of Enterostomies in the Rat

“…The influences of nitrogen mustard [6], thio-TEPA [8], cyclophosphamide [15], adriamycin [3] and methotrexate [2] on wound heal ing have been described.…”