Effect of the route of benzo[a]pyrene administration on sister chromatid exchange and DNA binding in bone marrow of mice differing with respect to cytochrome P450 1A1 induction.
The effects of the route of benzo[a]pyrene administration on sister chromatid exchange (SCE) and B[a]P diol epoxide (B[a]PDE)-DNA adducts formation in bone marrow cells of Ah responsive (C57BL/6; B6) and Ah non-responsive (DBA/2; D2) mice were determined. Animals were treated intraperitoneally (i.p.), intragastrically (i.g.) or topically with two 100 mg/kg doses of benzo[a]pyrene 24 h apart and killed 96 h after the first treatment. Significant increase in the frequencies of SCE and the level of B[a]PDE-DNA adducts as measured by synchronous fluorescence spectrophotometry were detected in D2 mice as compared to B6 mice. The route of administration had little effect on SCE levels in bone marrow cells in D2 mice. In B6 mice higher levels of SCE were observed following i.p. administration as compared to i.g. or topical administration. In both strains the highest level of B[a]PDE-DNA adducts was formed after i.p. administration of B[a]P. We conclude that the i.p. route of B[a]P administration is the most effective in inducing SCE and B[a]P-DNA adducts formation. SCE induction does not correlate linearly with the amount of B[a]PDE-DNA adducts formed in these cells after administration of the above dose of B[a]P.
Brauze
D
D
Institute of Human Genetics, Polish Academy of Sciences, Poznan.
Wielgosz
S M
SM
Pawlak
A L
AL
Baer-Dubowska
W
W
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism*; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage* / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D004333:Drug Administration Routes; D004790:Enzyme Induction; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009153:Mutagens / Q000008:administration & dosage* / Q000378:metabolism; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D018736:DNA Adducts; D009153:Mutagens; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA; D019363:Cytochrome P-450 CYP1A1