Efficacy of i.v. or i.p. injected cytotoxic drugs on proliferating and non-proliferating hair follicles of the mouse.
A range of drug doses of Adriamycin (ADR), Actinomycin-D (ACT-D), and Mitomycin-C (MMC) were given i.v. or i.p. to mice 1 day after a priming dose of radiation to elicit epilation response. The hair follicles were stimulated through plucking 11 days before irradiation or were unstimulated to represent proliferating and nonproliferating populations. The maximum epilation that appears at 8 days or at 8.5 weeks for proliferating and nonproliferating follicles was quantified using a subjective scale. In general, the i.v. route of administration was more effective than i.p. for all three drugs. Proliferating follicles were more susceptible than non-proliferating follicles to the action of drugs, especially ADR (p = .0001). Radiation doses which would give the same effect as ADR were calculated for proliferating follicles: 8 mg/kg given i.v. was equivalent to 4.6 (3.9, 5.2) Gy. For i.p. administration, 8 mg/kg was equivalent to only 0.6 (-0.1, 1.3) Gy. The in vivo assay of drug effect on hair follicles has advantages over LD10 as a model for toxicological investigation of new drugs: it can assess response of proliferating or non-proliferating cells of the same histotype and, in the case of proliferating follicles, it is quicker, thus enabling the use of doses higher than LD50 for bone marrow deaths.
Vegesna
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Department of Radiation Oncology, UCLA 90024-1714.
Withers
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HR
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002455:Cell Division; D003609:Dactinomycin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D006197:Hair / Q000187:drug effects* / Q000502:physiology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage
D000970:Antineoplastic Agents; D008937:Mitomycins; D003609:Dactinomycin; D016685:Mitomycin; D004317:Doxorubicin