Effect of dietary Aroclor 1254 exposure on lung and kidney cytochromes P450 in female rats: evidence for P4501A2 expression in kidney.
In this report, we have investigated the effect of dietary exposure to Aroclor 1254 (1-100 ppm) given chronically or discontinuously over an 84-day time interval to the female F344 rat. Cytochrome P4501A was quantified in lung and kidney by measuring the dealkylation of ethoxyresorufin substrate and by Western immunoblotting. P4501A displayed a dose- and time-dependent increase in both extrahepatic organs. The kidney appeared to be more responsive to induction than lung at all doses (maximum of 500-fold induction following 84 days exposure to 100 ppm). Further, there was evidence by enzymatic activity, immunoblotting and Northern analysis of total RNA for the presence of 1A2 in the most highly induced kidneys. The decline in 1A induction observed following discontinuous exposure was more prominent in the kidney than in the lung. These data demonstrate the sensitivity of kidney to P4501A induction capacity as compared to lung, although the persistence of the induction response was evident in lung and not kidney.
Beebe
L E
LE
Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA.
Fornwald
L W
LW
Alworth
W L
WL
Dragnev
K H
KH
Lubet
R A
RA
D000818:Animals; D001140:Aroclors / Q000008:administration & dosage / Q000633:toxicity*; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D020111:Chlorodiphenyl (54% Chlorine); D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004032:Diet; D004790:Enzyme Induction; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008861:Microsomes / Q000201:enzymology; D008969:Molecular Sequence Data; D009281:Naphthalenes / Q000494:pharmacology; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344
D001140:Aroclors; D002273:Carcinogens; D009281:Naphthalenes; D020111:Chlorodiphenyl (54% Chlorine); C065012:2-ethynylnaphthalene; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2