Induction of Liver Cell Adenomata in the Rat by a Single Treatment with N-Methyl-N-Nitrosourea given at Various Times after Partial Hepatectomy

Abstract

A single treatment of adult animals with the potent carcinogen NMU was known to induce tumours in a wide variety of organs, with the notable exception of liver. Administration of NMU after partial hepatectomy gave rise to the first liver cell adenomata ever observed in rats due to this carcinogen. The tumours were induced when NMU was given during the period of increased DNA synthesis but not when given early in the pre-replicative period. Although tumours were induced in other organs, the incidence of these did not correlate with the timing of NMU administration. It is suggested that replication of damaged DNA may be a relevant event in carcinogenesis. Images Fig. p507-a

The effect of isoprenaline on induction of tumours by methyl nitrosourea in the salivary and mammary glands of female wistar rats

“…The earliest time for macroscopic observation of kidney tumours was 19 weeks, and they were found frequently in animals dying 30 weeks or longer after treatment (Table II). In general the spectrum of tumours was similar to that observed by other authors (Craddock and Frei, 1974;Druckrey et al, 1967;Leaver et al, 1969). DISCUSSION A single i.v.…”

“…DNA synthesis was suggested as the critical factor both in croton oil stimulation of dimethylbenz(a)anthracene (DMBA)-induced murine epidermal tumours (Frei and Harsono, 1967) and in the induction of liver tumours by MNU in partially hepatectomized rats (Craddock and Frei, 1974). The response of the liver to such an insult is, however, both complex and prolonged (Harkness, 1957).…”

Primary cancer of the liver in Kenyan children

“…Newborn and young animals are often highly sensitive to hepatocarcinogens (Della Porta and Terracini, 1969). The same is true of adult animals whose livers are regenerating following partial hepatectomy (Craddock and Frei, 1974;Warwick, 1971b) or chemical damage (Craddock,1 976). It would seem that cells in cycle are more vulnerable to the action of hepatocarcinogens.…”

High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity

“…9,10 However, the use of epidemiologic and clinical predictors for the selection of patients to be surveyed would result in an inappropriate loss of target population, because each of these predictors identifies nonoverlapping HCC risk groups. Conversely, assessment of liver cell proliferation, which is a critical step in cancer development, 11,12 might help to better estimate HCC risk at the individual level. Bromodeoxyuridine uptake assay, 13 silver staining of nucleolar organizer region proteins (AgNOR), 14,15 immunostaining of Ki67, 16 and proliferating cell nuclear antigen (PCNA) 17 have been employed for assessing liver cell proliferation in patients with chronic liver diseases, because these assays are applicable to archival specimens.…”