High inducibility of mouse renal CYP2E1 gene by tobacco smoke and its possible effect on DNA single strand breaks.
Several studies have shown in humans an association between renal carcinoma and cigarette smoking. Cigarette smoke contains numerous cytochrome P450 inducers and substrates. In the present study we investigated the effect of cigarette smoke on the regulation of murine cytochrome P450 expression in kidney and its possible role in the induction of single strand breaks in DNA. Results demonstrated that CYP2E1 (activity, protein, and MRNA) was induced by tobacco smoke (2.1, 5.6 and 20.8, respectively). We did not detect any CYP1A, CYP2B, and CYP3A using Western blot and RT-PCR experiments. We have analyzed the renal single strand breaks of DNA in control and treated mice. The results indicated an increase of single strand breaks of DNA in kidney from treated mice which paralleled the high inducibility of the CYP2E1. No significant difference was observed between lymphocytes (which expressed very low or undetectable cytochrome P450 levels) of control and treated mice.
Seree
E M
EM
URA CNRS 1924, EA 859: Laboratoire de Pharmacocinétique et de Toxicologie, Faculté de Médicine, Marseille, France.
Villard
P H
PH
Re
J L
JL
De Meo
M
M
Lacarelle
B
B
Attolini
L
L
Dumenil
G
G
Catalin
J
J
Durand
A
A
Barra
Y
Y
D000818:Animals; D001483:Base Sequence; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D017931:DNA Primers; D004277:DNA, Single-Stranded; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000201:enzymology; D008969:Molecular Sequence Data; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012016:Reference Values; D014028:Tobacco Smoke Pollution
D017931:DNA Primers; D004277:DNA, Single-Stranded; D014028:Tobacco Smoke Pollution; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating