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Early Appearance of Serum -Fetoprotein during Hepatocarcinogenesis as a Function of Age of Rats and Extent of Treatment with 3'-Methyl-4-dimethylaminoazobenzene¹

Experimental Pathology Branch, National Cancer Institute, Bethesda, Maryland 20014

An embryonic serum globulin, -fetoprotein, was thought to be associated chiefly with overt liver cancer in man and animals. However, administration of 0.06% 3'-methyl-4-dimethylaminoazobenzene, a hepatocarcinogen, in the diet of 6- to 12-week-old male rats led to the prompt appearance of -fetoprotein in the serum of all of the animals within 3 to 4 weeks. Watabe (37) recently reported essentially similar findings with 4-dimethylaminoazobenzene. Discontinuation of the carcinogen at Week 5 dropped the -fetoprotein in serum to undetectable levels within 2 weeks, and it remained negative over a 30-week period of observation when, at autopsy of all rats in the group, no liver cancer was found. Administration of azo dye to 6-week-old rats for 10 weeks also decreased -fetoprotein in serum to undetectable levels over the next 2 weeks, except in 2 of 45 rats developing large hepatoma early; these remained positive. In the remainder of the rats in this group, -fetoprotein reappeared beginning at Week 15, and liver cancer was present in them at Week 20, except for 13 rats that remained negative, although 7 of them had hepatoma.

The age of the rats played no significant role in the precocious appearance of -fetoprotein, although rats aged 9 or 15 months generally displayed a positive serum -fetoprotein only at Week 4, somewhat later than 6-week-old rats. In these older groups fed carcinogen even for 10 weeks, -fetoprotein remained negative for the remainder of the test period of 30 weeks, except for 2 rats which had positive sera and hepatoma, and 1 rat which had hepatoma but had negative serum. Older rats are less sensitive to carcinogen.

The presence of -fetoprotein in each group of rats was related to the histological picture of the liver at the time of autopsy. There was no detectable -fetoprotein in untreated control rats, nor was there any in rats fed 0.05% of the hepatotoxic but not carcinogenic -naphthylisothiocyanate, which led to extensive jaundice and bile duct proliferation.

¹ Presented in part at the 63rd Annual Meeting of the American Association for Cancer Research, Boston, Mass., May 1972 (17).

² This work was undertaken at the National Cancer Institute during the tenure of a Research Training Fellowship (awarded by the International Agency for Research on Cancer, Lyon, France) while the recipient was on leave of absence from the Laboratory of Pathology, Rijks Instituut voor de Volksgezondheid, Bilthoven, The Netherlands (his present address).

³ To whom requests for reprints should be sent, at the National Cancer Institute, Building 37, Room 3B27, Bethesda, Md. 20014.

Received 1/14/72. Accepted 4/ 5/72.