Use of precision-cut liver slices for studies of unscheduled DNA synthesis.
Precision-cut liver slices were prepared from untreated and Aroclor 1254 (ARO)-treated male Sprague-Dawley rats with a Krumdieck tissue slicer. Liver slices were cultured for 24 hr in medium containing [3H]thymidine and 0-0.1 mM 2-acetylaminofluorene (2-AAF) using a dynamic organ culture system and processed for autoradiographic evaluation of unscheduled DNA synthesis (UDS). Compared with control (i.e. 0 mM 2-AAF) liver slice cultures, 2-AAF produced a concentration-dependent increase in UDS, the effect being more marked in liver slices from ARO-treated than from untreated rats. With liver slices from untreated rats, 2-AAF produced the greatest increase in UDS in centrilobular hepatocytes. 2-AAF-induced UDS in liver slices from ARO-treated rats was most marked in centrilobular hepatocytes but the effect also extended to other areas of the liver lobule. These results demonstrate that precision-cut liver slices may be a valuable alternative in vitro system to hepatocyte cultures for screening chemicals for potential genotoxicity. Unlike hepatocyte cultures, liver slices permit the study of zonal differences in UDS. Moreover, this technique could be applied to other tissues and the study of species differences in response.
Beamand
J A
JA
BIBRA Toxicology International, Carshalton, Surrey, UK.
Price
R J
RJ
Blowers
S D
SD
Wield
P T
PT
Cunninghame
M E
ME
Lake
B G
BG
D015073:2-Acetylaminofluorene / Q000633:toxicity; D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004247:DNA / Q000032:analysis; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D006652:Histological Techniques; D008099:Liver / Q000737:chemistry*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001140:Aroclors; D020111:Chlorodiphenyl (54% Chlorine); D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene