thiouracil and Skin-Neoplasms

Blood pharmacokinetics and tissue distribution of 5-dihydroxyboryl-6-propyl-2-thiouracil (BPTU), a boron carrier with postulated melanin-seeking properties for boron neutron capture therapy, were determined in C57/BL mice with subcutaneous pigmented or non-pigmented B16 melanomas. Borocaptate sodium (BSH) was used as a boron compound without melanin-seeking properties in a comparative biodistribution study in the same animal tumour models. Administration of single doses showed that BPTU was retained better in the pigmented B16 tumour than in the non-pigmented variant. BPTU was found in large concentrations in kidney and liver. Brain boron was approximately 10-fold lower than tumour boron. On a molar basis, BPTU demonstrated higher affinity for B16 tumours than BSH. Owing to solubility limits, tumour boron concentrations in this mouse study were too low for effective application of BNCT. However, the high tumour-to-blood and tumour-to-normal tissues ratios indicate that, with appropriate formulation, BPTU could be a promising candidate for clinical BNCT.

Topics: Animals; Borohydrides; Boron Compounds; Boron Neutron Capture Therapy; Brain Neoplasms; Melanins; Melanoma, Experimental; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Propylthiouracil; Skin Neoplasms; Sulfhydryl Compounds; Thiouracil; Tissue Distribution

Previous studies have demonstrated that retinoids possess antineoplastic properties against melanoma. The purpose of this study was to determine whether topically applied retinoic acid could prevent melanoma development in syngeneic mice after intracutaneous cell inoculation. Trans-retinoic acid in DMSO was applied daily for 28 days after melanoma implantation and tumor growth was quantitated by the uptake of [14C]thiouracil, a tracer compound specific for melanoma which is incorporated linearly according to the weight of the tumor. Marked reduction in tumor growth was noted at the highest concentration (0.1%) tested and lesser but significantly decreased tumor growth patterns were also realized at lower concentrations in a dose-dependent manner. Thus, topically applied retinoic acid is capable of inhibiting S91 melanoma growth in vivo.

Topics: Administration, Topical; Animals; Carbon Radioisotopes; Dimethyl Sulfoxide; Dose-Response Relationship, Drug; Male; Melanoma; Mice; Mice, Inbred DBA; Neoplasm Transplantation; Skin Neoplasms; Thiouracil; Tretinoin

Topics: Animals; Fundulidae; Growth and Development; Melanoma; Melanoma, Cutaneous Malignant; Melanoma, Experimental; Skin Neoplasms; Thiouracil; Thyroxine

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anthracenes; Benz(a)Anthracenes; Carcinogens; Croton Oil; Mice; Skin Neoplasms; Thiouracil; Thyroxine