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The Effects of the Time Interval and Sequence of the "Initiating" and "Promoting" Stimuli on the Tumor Yield^*

( Department of Medicine and Surgery, Ontario Veterinary College, Guelph, Canada)

1. C57BL/C3H mice of both sexes were exposed to one, two or three "initiating" treatments of a 0.25 per cent solution of 9,10-dimethyl-1,2-benzanthracene (DMBA).

2. In all groups the "promoting" treatment consisted of 33 applications of a croton seed extract (DJ-10), beginning on the 7th, 37th, or 67th day after the first DMBA exposure, and therefore either following "initiating" treatments or alternating with them.

3. A direct relationship between the number of tumors induced and the number of "initiating" stimuli resulted.

4. Alternating exposures to the "initiating" and "promoting" stimuli were more effective in inducing tumors than when the latter stimuli followed the former.

5. The significance of the results was discussed in the light of the two-stage mechanism of carcinogenesis.

^* This work was supported in part by a grant-in-aid from the National Cancer Institute of Canada.

Received 7/ 7/58.