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Selective loss of pulmonary cytochrome P-450I in rabbits pretreated with polychlorinated biphenyls
Abstract:
The polychlorinated biphenyls mixture, Aroclor 1254, generally considered a powerful inducer of rat hepatic and pulmonary microsomal monooxygenases, caused a 70% decrease in ethylmorphine N-demethylase activity, a 31% decrease in benzo(a)pyrene hydroxylase activity, and a 42% decrease in cytochrome P-450 content in rabbit lung microsomes. When pulmonary cytochrome P-450 was solubilized and subjected to column chromatography, the elution profiles of the two forms of the hemeprotein showed a marked decrease in cytochrome P-450I in treated rabbits, with no significant alteration in cytochrome P-450II content. These data were confirmed by subjecting the two cytochromes to gel electrophoresis and staining the electrophoretic bands for protein and heme-associated peroxidase activity. Cytochromes P-450I and P-450II isolated from Aroclor 1254-treated rabbits showed differences in spectral properties as well as in their stabilities. The CO difference spectral determinations showed absorbance maxima at 452 and 450 nm for cytochromes P-450I and P-450II, respectively. At room temperature, cytochrome P-450II was much more stable than P-450I. The present studies provide evidence not only for species differences in the biological actions of the polychlorinated biphenyls but also demonstrate differential effects of the environmental pollutant on the two major forms of cytochrome P-450 and associated enzymic activities in rabbit lungs.
Insights
Aroclor 1254, a polychlorinated biphenyls mixture, significantly reduced cytochrome P-450 enzyme activity in rabbit lungs. This environmental pollutant differentially affected two major cytochrome P-450 forms, impacting their stability and spectral properties.
Area of Science:
- Biochemistry
- Toxicology
- Environmental Science
Background:
- Polychlorinated biphenyls (PCBs) are environmental pollutants known to affect biological systems.
- Aroclor 1254 is a specific PCB mixture often studied for its effects on enzyme induction.
Purpose of the Study:
- To investigate the effects of Aroclor 1254 on cytochrome P-450 enzyme activities and content in rabbit lung microsomes.
- To determine if Aroclor 1254 differentially affects different forms of cytochrome P-450.
Main Methods:
- Treatment of rabbits with Aroclor 1254.
- Assay of ethylmorphine N-demethylase and benzo(a)pyrene hydroxylase activities.
- Measurement of cytochrome P-450 content.
- Solubilization, column chromatography, gel electrophoresis, and spectral analysis of cytochrome P-450 forms.
Main Results:
- Aroclor 1254 caused significant decreases in ethylmorphine N-demethylase (70%), benzo(a)pyrene hydroxylase (31%), and total cytochrome P-450 content (42%) in rabbit lung microsomes.
- Column chromatography revealed a marked decrease in cytochrome P-450I content with no significant change in cytochrome P-450II.
- Isolated cytochromes P-450I and P-450II exhibited different spectral properties and stabilities, with P-450II being more stable.
Conclusions:
- The study demonstrates differential effects of Aroclor 1254 on the two major forms of cytochrome P-450 in rabbit lungs.
- These findings highlight species differences in the biological actions of polychlorinated biphenyls and their specific impacts on xenobiotic-metabolizing enzymes.