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Sequential Histological and Histochemical Study of the Rat Liver during Aflatoxin B₁-induced Carcinogenesis¹

Laboratorium voor Histochemie en Cytochemie, Departement Medische Navorsing, Fakulteit Geneeskunde, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium

Male Wistar rats were given 50 µg of aflatoxin B₁ twice aweek for 4 weeks, and thereafter 75 µg twice a week for 10weeks. Their livers were investigated histologically andhistochemically for glycogen, RNA, fat, alkaline and acidphosphatases, adenosine triphosphatase, 5'-nucleotidase,glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, succinic dehydrogenase, and alkaline and acid nucleases. No significant lesions occurred before 15 weeks.During this period, the liver was histochemically unchangedexcept for a periportal decrease of alkaline phosphatase andadenosine triphosphatase. Scattered hepatocytes with astrong glucose-6-phosphatase activity appeared. Thesechanges represent toxic effects of aflatoxin B₁ and areirrelevant to carcinogenesis. From 15 weeks onward, threetypes of liver cell hyperplastic foci and nodules developed.Histologically, and with respect to glycogen, fat, and RNAcontent, only two of these types were considered as potentialprecursors of hepatocarcinomas. However, all types exhibited a decrease or absence of the enzymes studied. Bothhistological and histochemical changes stressed the complexheterogeneity existing between and within hepatic foci andnodules. From 11 months on, hepatocarcinomas developed.The tumors disclosed similar histochemical changes. Thissimilarity further supports the "precarcinomatous" natureof hyperplastic foci and nodules. It appears that focalchanges in surface as well as in cytoplasmic and nuclearenzymes are intimately and very early linked to thecarcinogenic process. Whether they are fundamental oronly represent an epiphenomenon remains unclear.

¹ Paper 2 of a series of 2. Paper 1 is Ref. 22. This work was partially supported by a grant from the Fonds voor Wetenschappelijk GeneeskundigOnderzoek of Belgium. It was presented as an abstract at the SecondMeeting of the European Association for Cancer Research, Heidelberg,Germany, October 2 to 5 1973.

Received 9/ 1/73. Accepted 5/16/75.

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