Induction by cholera toxin of synchronous divisions in vivo in the epidermis resulting in hyperplasia.

Intracutaneous injection of cholera toxin, exotoxin of Vibrio cholerae, into the dorsal skin of mice, rats, and hamsters at doses of greater than 0.1 ng evoked an acute reaction at the site of injection, which was characterized histologically by an edematous reaction in the dermis and mitotic stimulation in the epidermis. Mitotic and labeling induces of basal cells of the mouse epidermis showed two peaks at 24 and 48 hr after injection, thereby producing epidermal hyperplasia. The thickness of the intrafollicular epidermis increased progressively from 32 hr after toxin injection, being greatest on day 4 and decreasing to normal on day 7. The epidermis on day 4 after injection of 1.0 ng of toxin was about 4- to 6-fold thicker than normal or phosphate buffer-treated control skin. This sequence of events indicated that cholera toxin induced two successive synchronous divisions of the epidermal cells and produced temporary hyperplasia without interfering with epidermal differentiation. The complete structure and function of the cholera toxin are required for induction of epidermal hyperplasia: no mitotic stimulation was induced by injection of the A and B units of the cholera toxin molecule or by preincubation of the toxin with anti-cholera toxin antibody and with the membrane receptor, GM1 ganglioside. Five other agents known to increase the level of intracellular cyclic AMP by different means (dibutyryl cyclic AMP, 3-isobutyl-1-methylxanthine, theophylline, isoproterenol, and prostaglandin E1) did not produce a skin reaction.