Reversal of phenobarbital-induced hyperplasia and hypertrophy in the livers of lpr mice.
Fas is a cell surface receptor that mediates apoptosis, and Fas mRNA has been demonstrated in hepatocytes. MRL/MP-lpr/lpr mice carry the mutated lymphoproliferation-associated gene, lpr, that codes for truncated Fas protein, resulting in reduced apoptotic potential in some circumstances. Phenobarbital treatment of experimental animals induces cytochrome P450 enzymes, and thus acts as a growth stimulus to the liver with both hyperplasia and hypertrophy; cessation results in reversion of liver to normal size with apoptosis playing a role. This study has determined the respective contributions of atrophy and apoptosis to this involution in Fas-defective and normal-FAs bearing animals. Between the first day and the fifth day after phenobarbital cessation, the weights of both Fas-defective (lpr/lpr) livers and control (lpr/+) livers reduced. Hepatocyte hypertrophy gradually reverted in both categories of mouse and this was the greater contribution to reduction in liver size. In lpr/lpr animals, there was a consistent level of apoptosis which remained relatively constant, while numbers of apoptotic cells in control livers increased over the period. This investigation has shown that in liver, a mechanism to execute apoptosis is operative even in Fas-defective mice, but it is not sensitive to signals activated by the removal of the growth stimulus. This is in contrast to mice which can mount a Fas-mediated response; thus a separate apoptotic pathway is indicated.
Sarraf
C E
CE
Department of Histopathology, RPMS, Hammersmith Hospital, London, UK.
Horgan
M
M
Edwards
R J
RJ
Alison
M R
MR
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D006984:Hypertrophy / Q000139:chemically induced / Q000473:pathology; D007124:Immunoenzyme Techniques; D008099:Liver / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009929:Organ Size; D010634:Phenobarbital; D019014:fas Receptor / Q000502:physiology*
D019014:fas Receptor; D010634:Phenobarbital