Papilloma Induction in Different Aged Skin Grafts to Young Recipients

Abstract

THE incidence of malignancy in lymphoid tissue increases with age in BALB/c mice¹. This could reflect either a deterioration of the immune surveillance mechanisms of the animals or there may be an increasing rate of malignant transformation of lymphoid cells with increasing age. Some evidence for the latter suggestion has been obtained by transferring lymphoid cells from old and young non-malignant syngeneic donors to young BALB/c recipients. Reticular tumours developed with an incidence that was three times higher in recipients of old cells than in mice which received young cells¹. Interpretation of my results, however, was limited by an inability to determine whether the tumours were derived from donor cells or host cells. In an attempt to overcome this problem I have investigated here tumour development on skin grafts transferred from old and young syngeneic donors to young recipients. Inbred BALB/c mice were used. A dorsal skin graft measuring 2 × 3 cm was placed on the back of each recipient with the graft hair pointing in the opposite direction to that of the recipient hair. Donor and recipient were of the same sex. All recipients were 2 months old when grafted and the donors either 14 or 2 months old. Twelve months later 25 µl. of acetone containing 40 µg ml.−1 of 7,12-dimethylbenz[α]-anthracene (DMBA) was applied once to the depilated graft. The phase of the hair cycle was checked before treatment with DMBA by observing the growth (or absence of growth) of the hair stubs for 5 days after dyeing the hair. Papillomas first appeared on the grafts 4 weeks after the application of DMBA, and 3 weeks later the maximum number of papillomas had appeared. Approximately 60% of grafts from old donors and 25 % of grafts from young donors bore papillomas (Table 1). Five months after DMBA treatment 80% of papillomas had regressed. Two months after the application of DMBA four carcinomas appeared on skin from an old donor and one on the skin from a young donor. No tumours developed on 35 male and 30 female mice bearing skin grafts treated with acetone only. This indicated an age dependent susceptibility of skin to a chemical carcinogen. The recipient mice were all of the same age, so that a decline in immune responsiveness with advancing age^2–4 alone could not account for the difference in susceptibility of skin from old and young donors. Although the growth cycle of hair can greatly influence chemical carcinogenesis^5–7, the number of mice in resting phase or growth phase was approximately the same in all groups, and I suggest that my results were not affected by this factor. The rate of skin sebum secretion may decrease with age and result in retention of a higher proportion of the applied carcinogen than in younger animals⁷. This may have increased the sensitivity of skin from old mice. It is unlikely to be the sole cause, as results have been obtained with lymphoid tumours¹; lymphocytes transferred from old donors to young recipients resulted in a higher incidence of spontaneous lymphoid tumours than transfer from young donors.