The
DNA-binding agents
daunomycin (DAU-NO),
mithramycin (MITH),
dactinomycin (ACT-D),
amsacrine (mAMSA) and
esorubicin (ESO) were tested for local
vesicant potential in a quantitative intradermal mouse skin model. Only MITH, which adlineates but doses not intercalate
DNA, did not produce dose-dependent skin ulcerations in the mouse. The
anthracycline antibiotics DAUNO and ESO produced the largest
skin ulcers when administered intradermally at clinically relevant doses (adjusted on the basis of comparable body surface areas). Numerous local pharmacologic adjuvants were tested for activity to decrease skin ulceration patterns in mice given one of the
DNA intercalators. Inactive local adjuvants included heat, cold, saline,
hyaluronidase, glucorticosteroids and isoproternol. Only one adjuvant, topical
dimethylsulfoxide (
DMSO), was found to reduce DAUNO skin lesions. A single topical
DMSO application significantly decreased ulceration size to almost half of control levels. However, it was ineffective for the other
intercalating agents. These results show that the
DNA intercalators DAUNO, ESO and ACT-D are potent
vesicants in a mammalian skin model. These
vesicant agents must be administered cautiously to prevent extravasation. No single local adjuvant treatment can be recommended for extravasation of these drugs in the clinic. One significant exception is DAUNO, where topical
DMSO may reduce clinical toxicities.