The modulating activity of interferon on benzo(a)pyrene bioactivation and clastogenesis in mice.
Acute intraperitoneal administration of benzo(a)pyrene (80 mg/kg b.wt.) resulted in time-dependent increases in chromosome aberrations, especially of break-type in the bone marrow of treated mice. Pretreatment with murine interferon-alpha/beta (5 x 10(4) IU daily for two days) caused a significative decrease in the cytogenetic response in vivo of benzo(a)pyrene (up to 51%) and a stabilization of aberrant cells up to 48 hr. The administration of murine interferon-alpha/beta 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 CYP1A1 level. Results suggest that the inhibition of benzo(a)pyrene hepatic metabolism by interferon was reflected by changes in its clastogenic activity. Persistence 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.
Hrelia
P
P
Department of Pharmacology, University of Bologna, Italy.
Morotti
M
M
Vigagni
F
F
Maffei
F
F
Paolini
M
M
Mesirca
R
R
Cantelli-Forti
G
G
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects*; D002869:Chromosome Aberrations; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007274:Injections, Intraperitoneal; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects; D016296:Mutagenesis / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D013997:Time Factors
D016898:Interferon-alpha; D001564:Benzo(a)pyrene; D016899:Interferon-beta; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1