Induction of CYP1A1 in rat lung cells following in vivo and in vitro exposure to quartz.
Respirable quartz has been classified as a human lung carcinogen, but the mechanism by which quartz exposure leads to lung cancer has not been clarified. Consistently higher risks of lung cancer are reported in smokers with quartz exposure and we therefore hypothesised that quartz exposure may alter the expression of enzyme systems involved in activation/detoxification of pre-carcinogens in cigarette smoke. More specifically we studied cytochrome P4501A1 (CYP1A1) expression using reverse transcriptase polymerase chain reaction and immunohistochemistry (IHC) upon in vitro and in vivo quartz exposure. In vitro incubation of rat lung epithelial cells with DQ12 quartz for 24 h showed a dose-dependent induction of CYP1A1-mRNA. On the other hand, CYP1A1 message was not increased in lung epithelial cells isolated from rats at 3, 28 or 90 days after intratracheal instillation of 2 mg DQ12. Following IHC for CYP1A1 protein in rat lung sections from later time-points (180 and 360 days), we observed an increase in the number of CYP1A1 positive cells. After in vivo quartz exposure, protein expression of the Aryl hydrocarbon receptor (AhR) was increased and nuclear translocation of AhR was observed at the same time-points. In conclusion, our findings demonstrate an effect of quartz exposure on chronic CYP1A1 expression in vivo, whereas the in vitro models show an immediate upregulation. We suggest that this upregulation of CYP1A1 may act as a co-carcinogenic pathway in quartz exposed workers by activation of pre-carcinogens such as those present in cigarette smoke.
Particle Research, Institut für Umweltmedizinische Forschung gGmbH an der Heinrich-Heine Universität, Dusseldorf, Germany.
Andrea
A
Becker
Catrin
C
Albrecht
Ad M
AM
Knaapen
Roel P F
RP
Schins
Doris
D
Höhr
Kirstin
K
Ledermann
Paul J A
PJ
Borm
D021581:Active Transport, Cell Nucleus; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004790:Enzyme Induction; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D011791:Quartz / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D000395:Air Pollutants, Occupational; D002273:Carcinogens; D018336:Receptors, Aryl Hydrocarbon; D011791:Quartz; D019363:Cytochrome P-450 CYP1A1