Biochemical, pathologic and morphometric alterations induced in male B6C3F1 mouse liver by short-term exposure to dichloroacetic acid.
Dichloroacetic acid (DCA) is a complete hepatocarcinogen and tumor promoter in the male B6C3F1 mouse. Published reports indicate that the compound is non-genotoxic. This study examines possible non-genotoxic (epigenetic) mechanisms by which DCA elicits its carcinogenic response. Correlative biochemical, pathologic and morphometric techniques are used to characterize and quantify the acute, short-term response of hepatocytes in the male B6C3F1 mouse to drinking water containing DCA. Cellularity, [3H]thymidine incorporation, DNA concentration, nuclear size, and binuclearity are evaluated in terms of level of exposure (0, 0.5 and 5 g/l) and length of exposure to DCA. The dose-related alterations in hepatocytes of animals exposed to DCA for 30 days or less indicate that short-term exposure to DCA results in inhibition of mitoses, alterations in cellular metabolism and a shift in ploidy class. Thus, DCA carcinogenesis may involve cellular adaptations, development of drug resistance and selection of phenotypically altered cells with a growth advantage.
Carter
J H
JH
Wood Hudson Cancer Research Laboratory, Newport, KY 41071-4701, USA.
Carter
H W
HW
DeAngelo
A B
AB
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004326:Drinking; D015726:Giant Cells / Q000166:cytology / Q000187:drug effects; D006984:Hypertrophy / Q000139:chemically induced; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D010641:Phenotype; D011897:Random Allocation; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D002273:Carcinogens; D004247:DNA; D003999:Dichloroacetic Acid; D013936:Thymidine