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 car cinogenesis study, using benzo(a)pyrene (BaP), diminished the experime ntal differences between exposed and control mice. A dose-related incr ease in noncollected mitotic index (n-mitotic index) was seen in kerat inocytes in the dorsal epidermis of mice which received four weekly tr eatments of BaP at 16, 32 and 64 mu g in 50 mu l of acetone. In contra st, the number of mitotic figures collected for 4 hr by Colcemid block (c-mitotic index) was depressed at 16 mu g, unchanged at 32 mu g, and elevated at 64 mu g of BaP. Weekly treatments with 4, 8 or 16 mu g Ba P 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 det ermining mitotic index depended upon dose and duration of treatment wi th BaP. The administration of Colcemid to acetone-treated mice increas ed the labeling index (number of labeled cells) and reduced the rate o f DNA synthesis (low grain count per keratinocyte nucleus). After chro nic application of BaP, Colcemid abrogated the increase in labeling in dex, but produced no additional effect on the number of grains per lab eled keratinocyte. The modifying effect of Colcemid was greatest when administered during the peak of the tissue response to BaP. A number o f significant changes in morphology of the skin associated with chroni c exposure to BaP were attenuated by the use of Colcemid. (C) 1996 Wil ey-Liss, Inc.