Species differences in response to peroxisome proliferators correlate in vitro with induction of DNA synthesis rather than suppression of apoptosis.

@article{James1996SpeciesDI,
  title={Species differences in response to peroxisome proliferators correlate in vitro with induction of DNA synthesis rather than suppression of apoptosis.},
  author={N. James and R. Roberts},
  journal={Carcinogenesis},
  year={1996},
  volume={17 8},
  pages={
          1623-32
        }
}
Tumorigenesis caused by the peroxisome proliferator (PP) class of non-genotoxic hepatocarcinogens is species restricted; rat and mouse are considered responsive whereas the available evidence suggests that humans, non-human primates, dogs, hamsters and guinea pigs are non-responsive. We have demonstrated previously that the PP, nafenopin can suppress rat hepatocyte apoptosis both in vitro and in vivo. Here we describe the ability of nafenopin to suppress apoptosis in mouse, hamster, guinea pig… Expand
The peroxisome proliferator nafenopin does not suppress hepatocyte apoptosis in guinea-pig liver in vivo nor in human hepatocytes in vitro
TLDR
The lack of response to nafenopin in guinea-pigs in vivo and human hepatocytes in vitro provides further evidence that these species may be refractory to the liver growth effects of PPs despite the ability of guinea/pigs and humans to respond to PPs by alterations in lipid metabolism. Expand
The rodent nongenotoxic hepatocarcinogen and peroxisome proliferator nafenopin inhibits intercellular communication in rat but not guinea-pig hepatocytes, perturbing S-phase but not apoptosis
TLDR
The findings are confirmed and extended by defining the time course of growth perturbation and by correlating this with species differences in loss of gap junctional intercellular communication (GJIC), which is associated with nongenotoxic carcinogenesis, possibly reflecting a tumour suppresser role of the connexins. Expand
Suppression of mouse hepatocyte apoptosis by peroxisome proliferators : role of PPARα and TNFα
TLDR
Examining the role of the peroxisome proliferator activated receptor α (PPARα) in mediating the suppression of apoptosis caused by PPs confirms the dependence of the response to PPs on PPARα and provides evidence that high concentrations of TNFα can modulate DNA synthesis and apoptosis in the absence of PPs. Expand
Species differences in response to diethylhexylphthalate: suppression of apoptosis, induction of DNA synthesis and peroxisome proliferator activated receptor alpha-mediated gene expression
TLDR
Promoter-reporter gene assays were used to compare the ability of MEHP to induce gene expression from the rat or the human ACO promoter to provide further weight of evidence at the cellular and molecular levels for a lack of risk to human health from the phthalate DEHP. Expand
Reduced expression of mature TGF beta 1 correlates with the suppression of rat hepatocyte apoptosis by the peroxisome proliferator, nafenopin.
TLDR
Data indicate that TGF beta 1 is involved during the onset of hepatocyte apoptosis and that the PP nafenopin can impinge on this cell death pathway, although more data are required to confirm this hypothesis. Expand
The non-genotoxic hepatocarcinogen nafenopin suppresses rodent hepatocyte apoptosis induced by TGFbeta1, DNA damage and Fas.
TLDR
The ability of nafenopin to protect hepatocytes from apoptosis is not restricted to species or apoptotic stimulus and it is possible, therefore, that the PPs may suppress apoptosis by acting on diverse signalling pathways, but it seems more likely that nafinopin suppresses hepatocyte apoptosis elicited by each death stimulus by impinging on a core apoptotic mechanism. Expand
Peroxisome proliferator-activated receptor alpha: role in rodent liver cancer and species differences.
TLDR
The effects of PPs and what is known of the molecular mechanisms of action and species differences with respect to rodents and man are described. Expand
Peroxisome proliferator-activated receptor alpha : role in rodent liver cancer and species di ff erences
Peroxisome proliferators (PPs) are chemicals of industrial and pharmaceutical importance that elicit liver carcinogenesis by a non-genotoxic mechanism. One of the intriguing properties of PPs is thatExpand
The perturbation of apoptosis and mitosis by drugs and xenobiotics.
TLDR
Recent data have demonstrated that PPs activate the PP-activated receptor alpha in rodent liver, leading to enzyme induction, stimulation of S-phase, and a suppression of apoptosis, which may lead to hepatocarcinogenesis in humans. Expand
Species differences in hepatic peroxisome proliferation, cell replication and transforming growth factor-beta1 gene expression in the rat, Syrian hamster and guinea pig.
TLDR
While peroxisome proliferators produce a wide spectrum of effects in rat liver, other species such as the Syrian hamster and guinea pig are less responsive and in the case of some endpoints (e.g., cell replication) may be refractory. Expand
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References

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Suppression of apoptosis has been implicated as a mechanism for the hepatocarcinogenicity of the peroxisome proliferator class of non- genotoxic carcinogens. The ability of the peroxisomeExpand
Comparison of the effects of nafenopin on hepatic peroxisome proliferation and replicative DNA synthesis in the rat and Syrian hamster.
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TLDR
While peroxisome proliferators produce hyperplasia in rat and mouse liver, these data suggest that they may not have any marked effect on hepatic replicative DNA synthesis in the Syrian hamster. Expand
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TLDR
The data presented here demonstrate that the clonal expansion of rodent hepatocytes in soft agar in response to peroxisome proliferators and EGF displays the same species differences as other pleiotropic responses to these compounds and is likely therefore to be relevant to the process of hepatocarcinogenesis. Expand
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TLDR
Interestingly, no apoptosis was seen in monolayer cells, suggesting that apoptosis in vitro is associated with cell shrinkage and detachment similar to that documented for the liver in vivo. Expand
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TLDR
Surprisingly, the majority of the hepatocytes generated during compound-induced hyperplasia were protected from apoptosis during liver regression, providing in vivo evidence to support the hypothesis that non-genotoxic hepatocarcinogens such as CPA and the peroxisome proliferators suppress apoptosis. Expand
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TLDR
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TLDR
The acutehyperplastic response induced by methylclofenapate was studied in several rodent species with different responsiveness to the hypertrophic and hyperplastic effects caused by this chemical, and it is indicated that the 2 x 2N cells responding to MCP undergo S-phase followed by amitotic cytokinesis to form 4N cells. Expand
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TLDR
The data demonstrate that hepatocytes maintained in vitro within an NPC coculture system retain differentiated function and the ability to respond to the peroxisome proliferator class of nongenotoxic carcinogens. Expand
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TLDR
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TLDR
The available experimental evidence suggests a strong association and a probable casual link between peroxisome-proliferator-elicited liver growth and the subsequent development of liver tumours in rats and mice. Expand
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