Metabolism of benzo[a]pyrene by cultured rat and human buccal mucosa cells
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Metabolism of benzo[a]pyrene by cultured rat and human buccal mucosa cells. / Autrup, Herman; Seremet, Tina; Bindslev, Dorthe Arenholt; Dragsted, Lars Ove; Jepsen, Arne.
In: Carcinogenesis, Vol. 6, No. 12, 1985, p. 1761-1765.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Metabolism of benzo[a]pyrene by cultured rat and human buccal mucosa cells
AU - Autrup, Herman
AU - Seremet, Tina
AU - Bindslev, Dorthe Arenholt
AU - Dragsted, Lars Ove
AU - Jepsen, Arne
N1 - (Ekstern)
PY - 1985
Y1 - 1985
N2 - Primary cultures of epithelial and fibroblast cells derived from human oral mucosa were studied for the ability to activate a tobacco smoke carcinogen, benzo[a]pyrene (BP). The cells were exposed to benzo[a]pyrene for 18 h. The cell-free medium was extracted with ethylacetate/acetone, and high-pressure liquid chromatography analysis of this fraction revealed that BP tetrols and diols were the major metabolites formed by both epithelial and fibroblast cells. However, the epithelial cells had a much higher rate of biotransformation of BP as measured by binding to cellular DNA. The mean binding level to human buccal mucosal DNA was among the highest observed in stratified human epithelia. The major BP - DNA adduct was formed by the reaction of the 'bay-region' BP diolepoxide with the exocyclic 2-amino group in guanine. In contrast to human cells, BP phenols and BP 9, 10-diol were the major metabolites produced by primary epithelial and fibroblast cells derived from rat buccal mucosa. The DNA binding levels of BP in the two rat cell types were identical, and the binding level was several-fold lower than in the human epithelial cells. When an established rat tongue epithelial cell line (RTE 2) was treated with polycyclic aromatic hydrocarbons - BP and 7,12-dimethylbenz[a]-anthracene - a slight toxic effect was observed. Our results indicate that primary cultures of oral mucosa are able to metabolize BP into its ultimate carcinogenic form at a rate similar to or higher than other potential target tissues for BP-induced carcinogenesis.
AB - Primary cultures of epithelial and fibroblast cells derived from human oral mucosa were studied for the ability to activate a tobacco smoke carcinogen, benzo[a]pyrene (BP). The cells were exposed to benzo[a]pyrene for 18 h. The cell-free medium was extracted with ethylacetate/acetone, and high-pressure liquid chromatography analysis of this fraction revealed that BP tetrols and diols were the major metabolites formed by both epithelial and fibroblast cells. However, the epithelial cells had a much higher rate of biotransformation of BP as measured by binding to cellular DNA. The mean binding level to human buccal mucosal DNA was among the highest observed in stratified human epithelia. The major BP - DNA adduct was formed by the reaction of the 'bay-region' BP diolepoxide with the exocyclic 2-amino group in guanine. In contrast to human cells, BP phenols and BP 9, 10-diol were the major metabolites produced by primary epithelial and fibroblast cells derived from rat buccal mucosa. The DNA binding levels of BP in the two rat cell types were identical, and the binding level was several-fold lower than in the human epithelial cells. When an established rat tongue epithelial cell line (RTE 2) was treated with polycyclic aromatic hydrocarbons - BP and 7,12-dimethylbenz[a]-anthracene - a slight toxic effect was observed. Our results indicate that primary cultures of oral mucosa are able to metabolize BP into its ultimate carcinogenic form at a rate similar to or higher than other potential target tissues for BP-induced carcinogenesis.
UR - http://www.scopus.com/inward/record.url?scp=0022339868&partnerID=8YFLogxK
U2 - 10.1093/carcin/6.12.1761
DO - 10.1093/carcin/6.12.1761
M3 - Journal article
C2 - 4064251
AN - SCOPUS:0022339868
VL - 6
SP - 1761
EP - 1765
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 12
ER -
ID: 254782426