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Bleomycin and cyclophosphamide toxicity in mice with damaged lung tissue
1Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin 78712-1074.
Toxicology
|July 3, 1989
Summary
Pretreating mice with butylated hydroxytoluene (BHT) significantly increased the toxicity of anticancer drugs bleomycin and cyclophosphamide (CP). This BHT pretreatment enhanced lung injury, particularly with bleomycin, suggesting a complex drug interaction impacting lung repair.
Area of Science:
- Toxicology
- Pulmonary Medicine
- Pharmacology
Background:
- Anticancer drugs like bleomycin and cyclophosphamide (CP) can cause lung damage and fibrosis.
- The impact of pre-existing lung damage on the toxicity of these agents remains under-investigated.
Purpose of the Study:
- To investigate the effect of butylated hydroxytoluene (BHT)-induced lung damage on the toxicity of bleomycin and cyclophosphamide (CP).
Main Methods:
- Male BALB/c mice were treated with BHT, CP, or bleomycin alone or in combination.
- Pulmonary DNA synthesis, mortality rates, and lung hydroxyproline content were analyzed.
- The timing of lung cell proliferation and sulfhydryl content were also assessed.
Main Results:
- BHT, CP, and bleomycin alone caused significant lung damage and cell proliferation.
- Pretreatment with BHT dramatically increased mortality when combined with bleomycin or CP.
- BHT and bleomycin combination increased lung fibrosis, while CP combination did not significantly elevate fibrosis beyond BHT alone.
- Bleomycin delayed BHT-induced lung cell proliferation, whereas CP attenuated it after initiation.
Conclusions:
- BHT pretreatment enhances the overall toxicity of bleomycin and CP.
- Lung injury is specifically exacerbated by the combination of BHT and bleomycin.
- The interaction with bleomycin may involve rapid inhibition of lung repair rather than oxidative stress.