Altered hepatic microsomal function and elevated protooncogene expression as residual effects in rats exposed to delta-9-tetrahydrocannabinol.
The microsomal activation of the potent hepatocarcinogen aflatoxin B1 (AFB1) and the expression of selected protooncogenes were investigated in the livers of rats exposed to delta 9-tetrahydrocannabinol (THC). At equimolar levels of cytochrome P-450, the microsome-mediated binding of AFB1 to DNA was significantly lower (56% of the controls) in preparations from drug exposed rats. Hepatic expression of the c-k-ras protooncogene was 3-fold higher in THC exposed animals. These results suggest the possible occurrence of long lasting residual effects in the rats exposed to THC.
Prasanna
H R
HR
Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR 72079.
Nakamura
K D
KD
Ali
S F
SF
Lu
M H
MH
Slikker
W
W
Hart
R W
RW
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011519:Proto-Oncogenes; D051381:Rats; D011919:Rats, Inbred Strains
D000348:Aflatoxins; D011518:Proto-Oncogene Proteins; D013759:Dronabinol; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D005982:Glutathione Transferase; D016283:Proto-Oncogene Proteins p21(ras)