The Modulating Activity of Interferon on Benzo(a)pyrene Bioactivation and Clastogenesis in Mice

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Abstract
Acute intraperitoneal administration of benzo(a)pyrene (80 mg/kg b.wt.) resulted in time‐dependent increases in chromosome aberrations, expecially of break‐type in the bone marrow of treated mice. Pretreatment with murine interferon‐α/β (5×104IU daily for two days) caused a significative decrease in the cytogenetic responsein vivoof benzo(a)pyrene (up to 51%) and a stabilization of aberrant cells up to 48 hr. The administration of murine interferon‐α/β gave rise to a marked depression of microsomal monooxygenase system after 24 hr, as exemplified by the significant reduction of cytochrome P450 content as well as deethylation of ethoxyresorufin. Interferon treatment delayed the obtainment of basal levels of oxidative metabolism to approximately 30 hr. After interferon plus benzo(a)pyrene treatment, ethoxyresorufin O‐deethylase activity showed a reduction up to 60%; levels comparable to benzo(a)pyrene treated group were restored by 48 hr. Immunoblotting analysis confirmed reduced CYPIA1 level. Results suggest that the inhibition of benzo(a)pyrene hepatic metabolsim by interferon was reflected by changes in its clastogenic activity. Persistance of low level of chromosome aberration at 48 hr may be reconducible to other interferon sensitive processes than effects on hepatic mixed‐function oxidase system, such as DNA repair activity and cell proliferation.

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