Tumour-associated hepatocellular mitosis in Ehrlich ascites tumour-bearing mice

The hepatocellular mitotic response associated with Ehrlich ascites tumour is mediated by the tumour less than 48 hr, but more than 18 hr prior to the time of observation (day 8 of tumour growth). Tumour-associated hepatocellular motisis is normally centrilobular in distribution and appears to involve marginally more of the liver lobule than is sensitive to the necrotic effect of CCl4. There is failure to summate mitotic activity when both tumour-associated hepatocellular mitosis and regenerative hepatocyte motisis would be expected to occur; in this situation regenreative heaptocyte mitosis is the overwhelming contributor to the observed mitotic index. It is postulated that tumour-associated hepatocellular mitosis is obligatorily centrilobular. Tumour-associated hepatocellular mitosis, on the evidence of the present work and the results of others using intraperitoneally administered proteolytic enzymes as inducers of hepatocyte mitosis, is considered to be systematically mediated; there is complete failure to observe any perilobar preponderance of mitotic activity. This implies an indirect effect of tumour in producing the hepatocyte mitogen. Criteria obtained from the present work are suggested as useful in any attempt to isolate and identify the true or in vivo tumour-associated mitogen, and would help to exclude possible non-specific mitogens.