The effect of essential fatty acid supplementation on keratinocyte replication.

Epidermal cell growth in culture, using the low calcium, low serum technique described by Boyce, is thought to induce rapid expansion by inducing an essential fatty acid (EFA) deficiency state. To determine the mechanisms whereby EFA deficiency induces increased epidermal cell growth, keratinocytes were passaged into medium without or with the addition of EFAs, 18:2(n-6), 20:4(n-6). The resulting populations were assayed for replication rate, differentiation, and plating efficiency. Supplemental EFAs significantly decrease keratinocyte culture expansion. This is evidenced by an increase in generation time, a decrease in thymidine incorporation, and a decrease in modeled replication rate. EFA supplementation also increased the expression of cornified cell envelopes. Serum-free medium induces EFA deficient keratinocytes that demonstrate increased replication and decreased differentiation. Restoration of EFAs reverses these changes. It may be possible to manipulate keratinocyte physiology using fatty acid modifications.