During chemical
carcinogenesis Langerhans cells (LC) are depleted from the epidermis, disrupting the normal immunological functions of the skin.
Tumor promotors but not initiators, have been shown to deplete
adenosine triphosphatase (
ATPase)-positive LC from the skin and therefore the cutaneous immune system may be impaired during
tumor promotion but not initiation. The present study shows that the
tumor promotor 12-O-tetradecanoylphorbol 13-acetate (TPA) but not the initiator
urethane depletes Ia-positive LC from BALB/c murine ear epidermis, and
beta-glucuronidase-positive LC from C57BL mouse tail skin. Sensitization with 2,4-dinitrofluorobenzene (
DNFB) through
urethane-treated skin resulted in a normal
contact sensitivity response when the mice were challenged 5 days later. In contrast, tolerance resulted from sensitization through TPA-treated skin as a result of the generation of suppressor cells. In addition, TPA but not
urethane-treated C57BL mouse tail skin survived for an extended time when grafted onto histoincompatible BALB/c mice. Therefore, impairment of the normal immunological functions of skin resulted from treatment with the
tumor promotor TPA but not the
tumor initiator urethane, which suggests that a loss of LC during
tumor promotion may impair immunological protection against skin
tumors.