Keratinocyte growth factor increases hair follicle survival following cytotoxic insult

Hair loss is a distressing side-effect of cancer therapy. Factors that migh t reduce this loss are therefore likely to improve patient well-being and r educe treatment refusal. Keratinocyte growth factor has been shown to regul ate proliferation and differentiation in epithelial tissues and may regulat e the clonogenic cells (stem cells) of the hair follicle. Using X-irradiati on as a model cytotoxic agent we investigated whether keratinocyte growth f actor pretreatment could increase hair follicle survival (by implication cl onogen survival) and regeneration of differentiated progeny (a hair). Irrad iated telogen follicle survival data were consistent with that published pr eviously. Daily keratinocyte growth factor pretreatment increased hair surv ival during the first hair growth cycle, the level of protection having a s light radiation dose dependence. Protec- tion was maintained after a second hair cycle, but at a lower level (hairs and follicles). Hairs irradiated i n anagen and analyzed during the second cycle exhibited a similar level of protection. No difference in protection levels could be observed between mi ce treated either once or twice daily with keratinocyte growth factor. Resu lts indicated approximately 10 extra hairs per mm(2) (14.5% of unirradiated control) could survive the cytotoxic insult if pretreated with 12.5 mu g k eratinocyte growth factor. This could be doubled by a 10 x higher keratinoc yte growth factor dose. The fact that protection was maintained during two cycles of hair growth indicated that the clonogenic cells had been protecte d. Keratinocyte growth factor pretreatment had no significant effect on the level of mitosis but increased the number of p21(waf1) expressing cells. I ntriguingly, the number of apoptotic fragments per follicle were transientl y increased in the keratinocyte growth factor pretreated mice, although thi s effect was most pronounced in the upper half of the follicle bulb, i.e., above (rather than within) the germinal matrix.