Dose response effects of 2-acetylaminofluorene on DNA damage, cytotoxicity, cell proliferation and neoplastic conversion in rat liver.

摘要: This study measured the effect of precise doses 2-acetylaminofluorene (AAF) in inducing DNA damage, functional changes and neoplastic conversion rat liver. Groups male F344 rats at 9 weeks age were exposed to cumulative 0.5 or 2.0 mmol AAF per kg body weight given by gavage daily 5 days week over an 8-week period maintained with no further exposure for up 8 weeks. Administration resulted formation N-deoxyguanosin-(8-yl)-2-aminofluorene liver relationship dose. In centrilobular hepatocytes zone glutamine synthetase-expressing cells was reduced exposure. By weeks, but not 4 higher two provoked increase cell proliferation immunohistochemical incorporation bromodeoxyuridine. Altered hepatocellular foci expressing placental form glutathione transferase induced high dose low At incidence 79 times that These highly proliferative. animals exposure, adducts decreased 80% subsided 80%, although synthetase remained diminished. After discontinuation AAF, number diminished 50% their indicating a phenotypic reversion many foci. With this protocol administration we have established non-linearity effects lack correlation between adduct induction cellular lesions. We suggest range those reported can be used contribution epigenetic genotoxic carcinogenesis threshold events.