TY - JOUR
T1 - Genetic differences in aryl hydrocarbon hydroxylase induction and benzo[α]pyrene produced tumorigenesis in the mouse
AU - Benedict, W. F.
AU - Considine, N.
AU - Nebert, D. W.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1973
Y1 - 1973
N2 - Aryl hydrocarbon (benzo[α]pyrene) hydroxylase induction in C57BL/6N and DBA/2N inbred mice and their progeny by aromatic hydrocarbons is most likely controlled by a single autosomal dominant trait in skin, peritoneal lining, and lung, as has been previously illustrated for induction of the enzyme in liver, kidney, and bowel; additional factors may influence the expression in skin, peritoneal lining, and lung, however. The susceptibility to tumorigenesis produced by the topical application of benzo[α]pyrene and promotion by phorbol ester or by the intraperitoneal administration of large doses of benzo[α]pyrene is not correlated with the genetically mediated presence or absence of the hydroxylase induction in littermates of back crosses and intercrosses among the C57BL/6N, DBA/2N, and NZW/BLN strains. Therefore, if this enzyme is necessary for metabolic activation of benzo[α]pyrene to the proximal carcinogen, the basal levels of the hydroxylase are sufficient. Compared with application of 7,12 dimethylbenz[α]anthracene directly to the skin, the intraperitoneal administration of the carcinogen is at least 25 times more effective in causing tumors at the site of promotion. This phenomenon may reflect either circulation of carcinogens metabolically activated by liver enzyme systems or circulation of existing viruses, perhaps subviral particles, activated by the parent polycyclic hydrocarbon molecule or its metabolism.
AB - Aryl hydrocarbon (benzo[α]pyrene) hydroxylase induction in C57BL/6N and DBA/2N inbred mice and their progeny by aromatic hydrocarbons is most likely controlled by a single autosomal dominant trait in skin, peritoneal lining, and lung, as has been previously illustrated for induction of the enzyme in liver, kidney, and bowel; additional factors may influence the expression in skin, peritoneal lining, and lung, however. The susceptibility to tumorigenesis produced by the topical application of benzo[α]pyrene and promotion by phorbol ester or by the intraperitoneal administration of large doses of benzo[α]pyrene is not correlated with the genetically mediated presence or absence of the hydroxylase induction in littermates of back crosses and intercrosses among the C57BL/6N, DBA/2N, and NZW/BLN strains. Therefore, if this enzyme is necessary for metabolic activation of benzo[α]pyrene to the proximal carcinogen, the basal levels of the hydroxylase are sufficient. Compared with application of 7,12 dimethylbenz[α]anthracene directly to the skin, the intraperitoneal administration of the carcinogen is at least 25 times more effective in causing tumors at the site of promotion. This phenomenon may reflect either circulation of carcinogens metabolically activated by liver enzyme systems or circulation of existing viruses, perhaps subviral particles, activated by the parent polycyclic hydrocarbon molecule or its metabolism.
UR - http://www.scopus.com/inward/record.url?scp=0015855044&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0015855044&partnerID=8YFLogxK
M3 - Article
C2 - 4123113
AN - SCOPUS:0015855044
SN - 0026-895X
VL - 9
SP - 266
EP - 277
JO - Molecular Pharmacology
JF - Molecular Pharmacology
IS - 2
ER -