Abstract
Cycylphosphamide (Cy) produces an interstitial pneumonitis in CBA mice. The extent of the lung damage has been quantified by measuring the increase in ventilation rate over 6 weeks after an i.p. injection of Cy 200, 250 and 300 mg/kg. A dose-dependent response was found. When a preliminary ("priming") dose of Cy at 50 mg/kg was given 7, 9 or 14 days before a single large dose of 250 mg/kg, lung damage was reduced, as shown by a smaller increase in ventilation rate than in those receiving 250 mg/kg alone, and this difference was significant (P less than 0.01) in the Day-14-and highly significant (P<0.001) in the Day-7-"primed" groups. When primed less than 7 days before, there was a relative increase in ventilation rate, which was statistically significant (P less than 0.01) in the Day-1-primed group. Similar effects were also seen in the survival of the mice.
Highlights
Summary.-Cyclophosphamide (Cy) produces an interstitial pneumonitis in CBA mice
INTERSTITIAL PNEUMONITIS and pulmonary fibrosis resulting from cyclophosphamide (Cy) administration in man is well documented, it is rare (Andre et al, 1967; Patel et al, 1976; Mark et al, 1978)
Cy priming has been shown to increase mouse survival after a second large dose of Cy, but neither the cause of death nor the mechanism of protection could be explained (Millar & McElwain, 1978). This is the first study in which the ventilation rate has been used as a functional assessment of the extent of druginduced lung damage
Summary
Twelve-week-old CBA male mice wrere used throughout the study. Groups of 5 mice I~ 9 were given Cy monohydrate Further groups of 5 mice were given a priming dose of 50 mg/kg Cy, from 14 days to 12 h before a second dose of. The rate of rise during the first 7 days after treatment appeared to increase with dose, and beyond 2 weeks the ventilation rate in mice given the lowest dose (200 mg/kg) declined, while that for the highest dose rates were examined over wNeekly periods. Pairs of mice were killed before, and 1, 2, 3, The mean ventilation rates following 250 mg/kg preceded by a single 50mg/kg priming dose, given 12 h to 14 days beforehand, are shown ini Fig. 2. In each panel of this figure the survival of the treated group of 5 mice is indicated: the and 4 weeks after a dose of 300 mg/kg of Cy. results are clearly less reliable when few. The mean ventilation rates of those mice primed at 7, 9 and 14
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