Skin tumor initiating activity of therapeutic crude coal tar as compared to other polycyclic aromatic hydrocarbons in SENCAR mice.

Crude coal tar (CCT), a complex mixture rich in polycyclic aromatic hydrocarbons (PAHs) including carcinogens such as benzo[a]pyrene (BP), is widely used therapeutically in dermatological practice, particularly in combination with ultraviolet radiation in the treatment of chronic dermatoses such as psoriasis. In this study we analyzed the tumor initiating activity of therapeutic CCT preparation (USP) in a two-stage model system (initiation and promotion) in SENCAR mice. The tumorigenicity of CCT was compared with other conventionally studied carcinogenic PAHs; 7,12-dimethylbenz[a]anthracene (DMBA), 3-methylcholanthrene (MCA), benzo[a]pyrene 7,8-diol (BP-7,8-diol) and benzo[a]pyrene (BP). A single topical application of an initiating dose of CCT (20 microliter), DMBA (39 nmol), MCA (746 nmol), BP-7,8-diol (352 nmol) or BP (396 nmol) was followed by twice weekly application of 12-O-tetradecanoylphorbol-13-acetate (TPA) (3.24 nmol). The first tumor appearance in the CCT treated group was at 6 weeks on test as compared with DMBA and MCA (3 weeks) and BP-7,8-diol and BP (4-5 weeks). In a total of 20 animals after 8 weeks on test the DMBA, MCA, BP-7,8-diol, BP and CCT groups of mice showed 457, 176, 106, 76 and 46 tumors, respectively. After 11 weeks 100% of the mice in each experimental group had developed tumors and the number of tumors/mouse was 24.3, 15.0 9.8, 6.6 and 3.3 in the DMBA, MCA, BP-7,8-diol, BP and CCT groups, respectively. These studies provide first evidence that a single topical application of a therapeutic preparation of CCT possesses skin tumor initiating activity.