The use of AHF in the rat as a predictive lesion for carcinogenesis has been frequently suggested. Regulatory agencies require that the data used to determine carcinogenic potential and for estimating risk cannot be open to different interpretations. The degree of uncertainty in establishing relationships between the different foci phenotypes, their fate, and the difference in results with different protocols precludes the use of these data is establishing carcinogenic hazard or in quantitative risk estimation.
ClaysonDB (1987). The need for biological risk assessment in reaching decisions about carcinogens. Mutat. Res.185: 243–269.
2.
ColumbanoALedda-ColumbanoBMLeeGRajalakshmiSSarmaDSR (1987). Inability of mitogen-induced liver hyperplasia to support the induction of enzyme-altered islands induced by liver carcinogens. Cancer Res.47: 5557–5559.
3.
EPA proliferative hepatocellular lesions of the rat: Review and future use in risk assessment. U.S. EPA Feb. 1986.
4.
EmmelotPSchererE (1980). The first relevant stage in rat liver carcinogenesis. A quantitative approach. Biochem. Biophys. Acta605: 247–304.
5.
EnzmannKHBannaschP (1986). Sequential phenotypic conversion of hepatocytes during carcinogenesis. Cancer Letts.30: S67.
6.
EstadellaMDPujolMJDomingoJ (1988). Cell phenotype instability in preneoplastic foci of rat liver. Carcinogenesis9: 563–566.
7.
FarberE (1980). The sequential analysis of liver cancer induction. Biochem. Biophys. Acta605:149–166.
8.
FarberE (1982). The biology of carcinogen-induced hepatocyte nodules and related liver lesions in the rats. Toxicol. Pathol.10: 197–205.
9.
GlauertHPSchwarzMPitotHC (1986). The phenotypic stability of altered hepatic foci: Effect of the short term withdrawal of phenobarbital and of the long term feeding of purified diets after the withdrawal of phenobarbital. Carcinogenesis7: 117–121.
10.
GoodmanDGWardJMSquireRAChuKCLinhartMS (1979). Neoplastic and non-neoplastic lesions in aging F344 rats. Toxicol. Appl. Pharmacol.48: 237–248.
11.
HanniganMHPitotHC (1985). Growth of carcinogen altered rat hepatocytes in the liver of syngenic recipients promoted with phenobarbital. Cancer Res.45: 6063–6070.
12.
HaradaTMaronpotRRMorrisRWStitzelKABoormanGA (1989). Morphological and stereological characterization of hepatic foci of cellular alteration in control Fischer 344 rats. Toxicol. Pathol.17(4) Pt 1: 579–593.
13.
HaradaTMaronpotRRMorrisRWBoormanGA (1989). Observations on altered hepatocellular foci in National Toxicology Program two-year carcinogenicity studies in rats. Toxicol. Pathol.17(4) Pt 1: 690–708.
14.
HirotaMWilliamsGW (1979). The sensitivity and heterogeneity of histochemical markers for altered foci involved in liver carcinogenesis. Am. J. Pathol.95: 317–328.
15.
HuitfeldtHSHuntJMPitotHCPoirierMC (1988). Lack of acetylaminofluorene-DNA adduct formation in enzyme altered foci of rat liver. Carcinogenesis7: 123–129.
16.
ItoNTsudaHTatematsuMInoueTTagawaYAokiTUwagawaSKagawaMOgisoT et al (1988). Enhancing effect of various hepatocarcinogens on induction of preneoplastic glutathione S transferase placental form positive foci in rats—An approach for a new medium-term bioassay system. Carcinogenesis9: 387–394.
17.
KitagawaT (1976). Sequential phenotypic changes in hyperplastic areas during hepatocarcinogenesis in the rat. Cancer Res.35: 2534–2539.
18.
Ledda-ColumbanoGMColumbanoAConiPLiguoriCPaniP (1987). Liver cell proliferation induced by the mitogen ethylene dibromide: Unlike compensatory cell proliferation, does not achieve initiation of rat liver carcinogenesis by diethylnitrosamine. Cancer Letts.36: 247–252.
19.
MaronpotRBoormanGA (1982). Interpretation of rodent hepatocellular proliferative alterations and hepatocellular tumors in chemical safety assessment. Toxicol. Pathol.10: 71–80.
20.
OgawaKOnoeTTakeuchiM (1981). Spontaneous occurrence of gamma glutamyl transpeptidase positive hepatocytic foci in 105 week old Wistar and 72 week old Fischer 344 male rats. J. Natl. Cancer Inst.67: 407–412.
21.
PitotHCSiricaAE (1980). The stages of initiation and promotion in hepatocarcinogenesis. Biochem. Biophys. Acta605: 191–215.
22.
PoppJAScortichiniBHGarveyLK (1985). Quantitative evaluation of hepatic foci of cellular alteration occuring spontaneously in Fischer 344 rats. Fundam. Appl. Toxicol.5: 314–319.
23.
PotterVR (1981). A new protocol and its rationale for the study of initiation and promotion of carcinogenesis in rat liver. Carcinogenesis2: 1375–1379.
24.
Van Der HeijdenCADormansJAMA (1981). A short-term induction of neoplastic nodules in the rat liver. II. Study of their development and effects of withdrawal of 2-acetylaminofluorene. Carcinogenesis2: 147–156.
25.
SargentLXuYHSattlerGLMeisnerLPitotHC (1989). Ploidy and karyotype of hepatocytes isolated from enzyme-altered foci in two different protocols of multistage carcinogenesis in the rat. Carcinogenesis10: 387–391.
26.
SchererEEmmelotP (1976). Kinetics of induction and growth of enzyme-deficient islands involved in hepatocarcinogenesis. Cancer Res.36: 2544–2554.
27.
SoltDBFarberE (1976). New principle for the analysis of chemical carcinogens. Nature263: 702–703.
28.
SoltDBMedlineAFarberE (1977). Rapid emergence of carcinogen-induced hyperplastic lesions in a new model for sequential analysis of liver carcinogenicity. Am. J. Pathol.88: 595–618.
29.
TatematsuMMeraYInoueTSatohKItoKSN (1988). Stable phenotypic expression of glutathione S-transferase placental type and unstable phenotypic expression of gamma glutamyltransferase in rat liver preneoplastic and neoplastic lesions. Carcinogenesis9: 215–220.
30.
WeberEMooreMABannaschP (1988). Enzyme histochemical and morphological phenotype of amphophilic foci and amphophilic/tigroid cell adenomas in rat liver after combined treatment with de-hydroepiandrosterone and N-nitrosomorpholine. Carcinogenesis9: 1049–1054.
31.
WilliamsGMWatanabeK (1978). Quantiative kinetics of development of N-2-fluornylacetamide induced altered (hyperplastic) hepatocellular foci resistant to iron accumulation and of their reversion or persistence following removal of carcinogen. J. Natl. Cancer Inst.61: 113–121.
32.
WilliamsGMMaruyamaHTanakaT (1987). Lack of rapid initiating or promoting or sequential syncarcinogenic effects of di-2-ethylhexylpthalate in rat liver carcinogenesis. Carcinogenesis8: 875–880.
33.
ZerbanHPreussmannRBannaschP (1989). Quantitative morphometric comparison between the expression of two different marker enzymes in preneoplastic liver lesions induced in rats with low doses of N nitrosodiethanolamine. Cancer Letts.43: 99–104.
34.
ZerbanHPreussmannRBannaschP (1988). Dose-time relationship of the development of preneoplastic liver lesions induced in rats with low doses of N-nitrosodiethanolamine. Carcinogenesis9: 607–610.