Effects of Methylglyoxal Bis(guanylhydrazone) on Skin Reactions in the Mouse after Fractionated Hyperthermic Exposures

Abstract

The modification of skin damage in the hind limb of the mouse produced by single and fractionated exposures to hyperthermia (430C) by methylglyoxal bis(guanylhydrazone) (MGBG) was studied. It was found that MGBG given intraperitoneally 4 hr prior to single heat exposure enhanced skin damage in a dose-dependent manner. Dose enhancement factors of 1.04, 1.23, and 1.41 were found for MGBG doses of 20, 40, and 80 mg/kg, respectively. Also, MGBG did not appear to modify the repair of subeffective heat damage in experiments in which MGBG was given 4 hr prior to each equal heat dose split over a 24-hr period. The amount of fractional repair of heat injury occurring within 24 hr was 0.94 for mice given only heat exposures, and 0.87 for mice receiving 40 mg/kg of MGBG prior to both heat exposures. However, in experiments in which longer time intervals were used between hyperthermic split doses (to 30 days after the initial exposure) and MGBG was given 4 hr prior to both heat exposures, it was found that the thermotolerant response occurring in mouse skin at about 2 to 4 days after exposure could be obliterated. MGBG appeared to have no effect on longterm repopulation occurring in mouse skin. Therefore, MGBG acts as a potentiating agent for early heat effects in skin and can also overcome thermotolerance expression in vivo.