Colcemid alters S phase and other parameters in skin during chronic exposure to benzo(a)pyrene

The administration of Colcemid for collecting mitotic figures in a carcinogenesis study, using benzo(a)pyrene (BaP), diminished the experimental differences between exposed and control mice. A dose-related increase in noncollected mitotic index (n-mitotic index) was seen in keratinocytes in the dorsal epidermis of mice which received four weekly treatments of BaP at 16, 32 and 64 micrograms in 50 microliters of acetone. In contrast, the number of mitotic figures collected for 4 hr by Colcemid block (c-mitotic index) was depressed at 16 micrograms, unchanged at 32 micrograms, and elevated at 64 micrograms of BaP. Weekly treatments with 4,8 or 16 micrograms BaP for 3-8 months induced an elevation in both n-mitotic and c-mitotic indices. The differences in results produced by the two methods of determining mitotic index depended upon dose and duration of treatment with BaP. The administration of Colcemid to acetone-treated mice increased the labeling index (number of labeled cells) and reduced the rate of DNA synthesis (low grain count per keratinocyte nucleus). After chronic application of BaP, Colcemid abrogated the increase in labeling index, but produced no additional effect on the number of grains per labeled keratinocyte. The modifying effect of Colcemid was greatest when administered during the peak of the tissue response to BaP. A number of significant changes in morphology of the skin associated with chronic exposure to BaP were attenuated by the use of Colcemid.