Formation and removal of dibenzo(a,e)fluoranthene-DNA adducts in mouse embryo fibroblasts

Journal Article · Sun Dec 01 04:00:00 EST 1985 · Carcinogenesis; (United States)

DOI:https://doi.org/10.1093/carcin/6.12.1791· OSTI ID:5632415

Perin-Roussel, O; Barat, N; Zajdela, F

In vivo binding of dibenzo(a,e)fluoranthene (DBF) to mouse embryo fibroblast DNA was compared with that observed previously in vitro on calf thymus DNA incubated with mouse liver microsomes. The h.p.l.c. elution patterns of the adducts formed by DBF metabolites with DNA and obtained in vivo at the optimal exposure time of 42-48 h were qualitatively very similar to the patterns obtained in vitro, but their amplitude was quantitatively reduced. There are two striking differences between the in vivo and in vitro results. Firstly, the most polar peak A, very abundant in vitro, was absent in vivo. Secondly, the reactivity of the two major proximate metabolites of DBF, the bay and pseudo-bay region dihydrodiols, was very different in intact cells compared with the results in vitro. When incubated in vitro, pseudo-bay region dihydrodiol DBF was twice as reactive as bay region dihydrodiol DBF. The opposite reactivities were observed in vivo. The major DBF-DNA adducts formed in vivo were collected in the peaks E, B and C. The predominant peak E contained DNA adducts of both bay and pseudo-bay region dihydrodiolepoxides which are the major ultimate metabolites of DBF in vivo and in vitro. The other two prominent peaks B and C contained DNA adducts of 3-hydroxy DBF pseudo-bay region dihydrodiolepoxide and the 7-hydroxy DBF bay region dihydrodiolepoxide, respectively. After adduct formation, post incubation of fibroblasts for a further 48 h, in the absence of DBF, eliminated half the amount of adducts present. Peak B adducts were repaired more efficiently than those of peaks E, C D and F. The carcinogenic initiating activity of DBF appears to be a complex process in which several DNA adducts play a role.

• OSTI ID: 5632415
• Journal Information: Carcinogenesis; (United States), Journal Name: Carcinogenesis; (United States) Vol. 12; ISSN CRNGD
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANIMAL CELLS
ANIMALS
AROMATICS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARCINOGENS
CHROMATOGRAPHY
COMPARATIVE EVALUATIONS
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
DNA
DNA ADDUCTS
DNA REPAIR
EMBRYOS
FIBROBLASTS
IN VITRO
IN VIVO
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
METABOLITES
MICE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
RECOVERY
REPAIR
RODENTS
SEPARATION PROCESSES
SOMATIC CELLS
VERTEBRATES