Induction of cytochrome P-450 in Sigmodon hispidus (cotton rats) exposed to dietary Aroclor 1254.
The induction of immunoreactive cytochrome P-450 protein and associated catalytic activities in 10-wk-old male and female Sigmodon hispidus (cotton rats) exposed for 2 wk to low dietary levels of Aroclor 1254 (0.33, 1.0, 3.3, 10, and 33 ppm), or the prototype P-450 inducers phenobarbital, DDT, clotrimazole, and beta-naphthoflavone was examined. Ethoxy-(ETR), methoxy- (MTR), pentoxy- (PTR), and benzyloxyresorufin (BZR) O-dealkylation activities were significantly increased at 0.33 ppm Aroclor for males and 1.0 ppm for females, when compared to control levels. O-Dealkylation activities peaked at 3.3 ppm for males and 10 ppm for females. ETR and MTR O-dealkylation activities were increased four- to eightfold while PTR and BZR O-dealkylation activities increased only two- to threefold. Liver/body weight ratios also increased, with the maximum ratios observed at the highest Aroclor dose, and were associated with histopathologic hepatocyte lesions. While increases in liver/body weight ratio, immunoreactive CYP2B protein, and BZR O-dealkylation were detected following phenobarbital treatment, no increase in PTR O-dealkylation activity was observed. These results demonstrate that S. hispidus (both males and females) are extremely sensitive to low dietary levels of Aroclor 1254, responding with increases in liver/body weight ratio, immunoreactive P-450 protein, and O-dealkylation activities. The cotton rat would appear to be a sensitive feral target species for detecting exposure to certain environmental contaminants.
Henneman
J R
JR
Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorp, NCI-FCRDC, MD 21702-1201.
Fox
S D
SD
Lubet
R A
RA
Ward
J M
JM
Nims
R W
RW
D000284:Administration, Oral; D000818:Animals; D001140:Aroclors / Q000008:administration & dosage / Q000633:toxicity*; D001822:Body Burden; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003640:Dealkylation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000378:metabolism; D012737:Sex Factors; D016205:Sigmodontinae; D015262:Xenobiotics / Q000633:toxicity
D001140:Aroclors; D002273:Carcinogens; D015262:Xenobiotics; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls