Dose-dependent induction of preneoplastic lesions by the tobacco-specific nitrosamine carcinogen NNK in the in ovo carcinogenicity assessment (IOCA) assay

Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie
H EnzmannGary M Williams

Abstract

The potential of the carcinogenic tobacco specific nitrosamine 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-1-butanone (NNK) to induce preneoplastic hepatocellular altered foci (HAF) was tested in the in ovo carcinogenicity assessment (IOCA) assay. Single doses of NNK over a dose range from 0.1 mg to 6 mg were injected into fertilized turkey eggs prior to incubation for 24 days. The livers were investigated by histological, histochemical and morphometric methods. Mortality was increased for eggs exposed to 6 mg. In this group, the whole livers were severely altered, showing pronounced changes of nucleus size and signs of cell death. At the dose of 2 mg various types of foci of altered hepatocytes (HAF) were observed. Basophilic cell foci of the solid or tubular type were most frequent. The NNK-induced HAF were very similar to the preneoplastic lesions that occur in the livers of mammals during hepatocarcinogenesis which are regarded as early indicators of carcinogenesis. The similarity to the HAF in rodents included histochemically detectable alterations like decreased activities of glucose-6-phosphatase, adenosine triphosphatase and glycogen phosphorylase. At doses of 1 mg or below, no HAF were detected. At all dose levels an in...Continue Reading

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Citations

Oct 15, 1998·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·H EnzmannG M Williams
Jun 29, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Gary M WilliamsUlrich Deschl

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