Hydroxyurea enhances methylnitrosourea skin tumorigenesis when given shortly before, but not after, the carcinogen

To study the relationship between epidermal DNA synthesis and carcinogenesis, hairless mice of both sexes were given a single topical application of 1 mg N-methyl-N-nitrosourea (MNU) in acetone. A control group received only MNU, whereas other groups were injected i.p. with 5 mg hydroxyurea (HU), 1 h, 45 min and 15 min before, simultaneously with, and 15 min, 30 min and 45 min after MNU application. The production of skin tumors was recorded and the results were assessed with accepted statistical methods. Injection of HU shortly before a single application of MNU enhanced skin carcinogenesis, and when HU is injected 30 min before MNU, the enhancement seems to be most pronounced. HU administered simultaneously with or following MNU application, did not alter the production of tumors. The cell kinetic situation in the epidermis at the time of a carcinogen application, and the modulation of the cell kinetic reaction to the carcinogen by any type of post- or pretreatment, may influence tumorigenesis.