Abnormalities in Liver Iron Accumulation During N-2-Fluorenylacetamide Hepatocarcinogenesis that are Dependent or Independent of Continued Carcinogen Action

Furuya, Keizo; Maeura, Yoshiichi; Williams, Gary M.

doi:10.1177/019262338401200204

Cited by 8 publications

(8 citation statements)

References 14 publications

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“…After cessation of AAF, a phenotypic reversion of IS-foci occurred, as described previously (6,47). This possibly suggests that some foci that developed during exposure depended on a promoting effect of the carcinogen, which ceased upon withdrawal.…”

Section: Methodssupporting

confidence: 65%

“…After cessation of AAF administration, some foci disappeared, as we have previously reported (6,47). In studies of foci induced by other carcinogens, this has been attributed to apoptosis (1,2,27).…”

Section: Methodssupporting

confidence: 60%

“…IS-was a sensitive marker of foci that developed during AAF exposure (6,15,46), whereas GGT activity was more distinct in foci during maintenance. PGT activity was also a constant property of foci, varying in intensity in early foci, but regularly distributed in advanced foci.…”

Section: Methodsmentioning

confidence: 93%

“…The suggestion by Enzmann and Bannach (5) that disappearance of early-appearing, severely altered foci is due to the nonspecific toxic effects of the carcinogen was also not supported by our study. We continue to propose that the reduction in foci after carcinogen removal is due largely to reacquisition of a normal phenotype mediated by the homeostatic influence of surrounding normal hepatocytes (6,42).…”

Section: Methodsmentioning

confidence: 95%

“…In Groups 1-10, 3 rats were sacrificed every week up to 10 wk. In Groups 11-13, after administration of AAF for 8 wk, rats were maintained on basal diet and sacrificed after a further 6,12 (32).…”

Section: Methodsmentioning

confidence: 99%

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Sequential Functional and Morphological Alterations During Hepatocarcinogenesis Induced in Rats by Feeding of a Low Dose of 2-Acetylaminofluorene

et al. 1994

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The early cellular events in liver carcinogenesis were studied in Fischer-344 male rats that either were fed 200 ppm 2-acetylaminofluorene (AAF) for up to 10 wk or were fed the carcinogen for 8 wk, the number again increased. IS -characterized the majority of foci during carcinogen administration, whereas after cessation of exposure, GGT+ and PGT+ foci predominated. None of the foci were positive for GS. After AAF exposure for 10 wk, a few neoplasms developed and greater numbers occurred after maintenance for a further 24 wk of rats exposed for 8 wk. We conclude the following: (a) the low dose of AAF caused subtle alterations in function and proliferation of normal hepatocytes and converted hepatocytes into focus cells; (b) reduction of the GS+ area is a sensitive indicator of cytotoxicity of AAF; (c) the development of some foci at an early stage depends on a promoting action of AAF, which ceased when the carcinogen was withdrawn, allowing some foci to undergo reversion; (d) a strong linkage exists in expression of IS-, GGT+, and PGT+ in foci; (e) the carcinogenic process accelerates in the absence of any indication of increased cytotoxicity by AAF; and (f) under the conditions of this study, no GS+ foci, adenomas, and carcinomas were found, indicating that no carcinogen-induced expression of GS occurred in these lesions and that GS expression is not linked to other phenotypic abnormalities.

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Section: Methodssupporting

confidence: 65%