Evidence for chemical carcinogenesis by multistage process

Phil Gunby
Arch Intern Med. 1981;141(12):1575. doi:10.1001/archinte.1981.00340130019005.
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A well-known two-phase method of inducing experimental skin tumors in mice involves application of a single dose of an "initiator" carcinogen, which probably triggers cell mutation, followed by repeated applications of a weak or totally noncarcinogenic "promoter."

But now investigators at the Oak Ridge (Tenn) National Laboratory and Michigan State University, East Lansing, say there is more to the process than that—with perhaps three stages in the promotion phase alone— and that this information may shed light on some possible tumor promoters in humans, and how to inhibit them.

Thomas J. Slaga, PhD, of the Oak Ridge facility, told an American Cancer Society seminar in Daytona Beach, Fla, that the first stage of the promotion phase seems to involve induction of primitive stem (embryonic phenotype) cells.

This is followed by morphological and biochemical changes in the skin during the second stage, he said, and then by epidermal hyperplasia during what


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