Studies of initiating stage of epidermal carcinogenesis in mice.

The earliest description of cancer has been traced back to records on Egyptian papyri of the fifteenth century B.C. Following this, in the era of Hippocrates, in the fourth century B. C., the nature of cancer was described as the presence of a tumour, and the absence of any tendency towards healing. Hippocrates used the term “kapkivos” , "carcinos”, for all indolent ulcers, and “kapkivwua”, "carcinoma” for progressive malignant tumours. In spite of many descriptions, and many personal views as to the origin of cancer in the following centuries, little came but mere speculation. Perhaps, the one of the most notable events in the history of cancer research was the essay by Bernard Peyrihle (1735-1804) of Lyon, “Qu’est ce que le cancer?”

Increased expression of c-fos, c-jun and LRF-1 is not required for in vivo priming of hepatocytes by the mitogen TCPOBOP

The notion that an increased expression of immediate early genes such as c-fos and c-jun is an absolute requirement for the G(0)-G(1) transition of the hepatocytes has recently been challenged by the finding that rat liver cell proliferation induced by primary mitogens may occur in the absence of such changes (Columbano and Shinozuka, 1996). To further investigate the relationship between immediate early genes and hepatocyte proliferation, we have compared the hepatic levels of c-fos, c-jun and LRF-1 transcripts during mouse liver cell proliferation in two conditions: (i) direct hyperplasia induced by the non-genotoxic hepatocarcinogen 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, and (ii) compensatory regeneration caused by a necrogenic dose of carbon tetrachloride. The results show striking differences in the activation of early genes. In spite of a rapid stimulation of S phase by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (approximately 8% of hepatocytes were BrdU-positive as early as 24 h after mitogen treatment versus 1% of labelled hepatocytes after 2/3 partial hepatectomy), no changes in the expression of c-fos, c-jun and LRF-1 could be observed. Moreover, no change in steady state mRNA hepatic levels of IGFBP-1 (a gene highly expressed in rat liver following partial hepatectomy), and only a slight increase in c-myc and PRL-1, was found after mitogen administration. On the contrary, a rapid, massive and transient increase in the hepatic mRNA levels of all these genes was observed during carbon tetrachloride induced regeneration. The results indicate that increased expression of immediate early genes may be dependent upon the nature of the proliferative stimulus, and it may not be a prerequisite in certain in vivo conditions such as proliferation induced in the absence of liver tissue damage