TY - JOUR
T1 - Ah receptor-independent induction of CYP1A2 gene expression in genetically inbred mice
AU - Gupta, Mona
AU - Miggens, John
AU - Parrish, Alan
AU - Womack, James
AU - Ramos, Kenneth S.
AU - Rodriguez, Louis V.
AU - Goldstein, Lawrence S.
AU - Holtzapple, Carol
AU - Stanker, Larry
AU - Safe, Stephen H.
N1 - Funding Information:
The financial assistance of the Electric Power Research Institute (contract WO-2963-04), the National Institutes of Health (ES04917), and the Texas Agricultural Experiment Station is gratefully acknowledged.
PY - 1998/5
Y1 - 1998/5
N2 - Acenaphthylene is a tricyclic aromatic hydrocarbon which induces hepatic methoxyresorufin O-demethylase (MROD) activity and CYP1A2 mRNA levels in 2 week-old male B6C3F1 mice. In the present study, this induction response was further investigated in genetically-inbred mice which differ in their aryl- hydrocarbon (Ah)-responsiveness. Acenapthylene (300 mg/kg) induced a 5- to 23-fold induction of MROD activity in Ah-nonresponsive (DBA and SJL) and responsive (C3H, C57/BL6, A/J, CBA and B6C3F1) mice. The highest induction response was observed in the DBA strain in which there was a 23- and 15-fold increase in activity in males and females, respectively. Acenaphthylene also caused a 2-fold increase in CYP1A2 mRNA and immunoreactive protein levels in 2 week-old DBA mice; however, this induction response was not observed in 6 week-old animals. For example, MROD activity in 6 week-old DBA mice was induced <2-fold by acenaphthylene, mainly as a consequence of increased basal CYP1A2 expression and MROD activity which, at the age of 6 weeks, approached levels induced by acenaphthylene in the 2 week-old mice. This was also observed by immunohistochemical staining with CYP1A2 antibodies of 2 and 6 week-old hepatic tissue from treated and control mice which also showed that CYP1A2 induction was dependent on the age of the animals.
AB - Acenaphthylene is a tricyclic aromatic hydrocarbon which induces hepatic methoxyresorufin O-demethylase (MROD) activity and CYP1A2 mRNA levels in 2 week-old male B6C3F1 mice. In the present study, this induction response was further investigated in genetically-inbred mice which differ in their aryl- hydrocarbon (Ah)-responsiveness. Acenapthylene (300 mg/kg) induced a 5- to 23-fold induction of MROD activity in Ah-nonresponsive (DBA and SJL) and responsive (C3H, C57/BL6, A/J, CBA and B6C3F1) mice. The highest induction response was observed in the DBA strain in which there was a 23- and 15-fold increase in activity in males and females, respectively. Acenaphthylene also caused a 2-fold increase in CYP1A2 mRNA and immunoreactive protein levels in 2 week-old DBA mice; however, this induction response was not observed in 6 week-old animals. For example, MROD activity in 6 week-old DBA mice was induced <2-fold by acenaphthylene, mainly as a consequence of increased basal CYP1A2 expression and MROD activity which, at the age of 6 weeks, approached levels induced by acenaphthylene in the 2 week-old mice. This was also observed by immunohistochemical staining with CYP1A2 antibodies of 2 and 6 week-old hepatic tissue from treated and control mice which also showed that CYP1A2 induction was dependent on the age of the animals.
KW - Acenaphthylene
KW - Ah receptor-independent
KW - CYP1A2 induction
KW - Mice
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U2 - 10.1016/S1382-6689(98)00004-0
DO - 10.1016/S1382-6689(98)00004-0
M3 - Article
C2 - 21781866
AN - SCOPUS:0031835388
SN - 1382-6689
VL - 5
SP - 205
EP - 213
JO - Environmental Toxicology and Pharmacology
JF - Environmental Toxicology and Pharmacology
IS - 3
ER -