A 13-week feeding study of butylated hydroxyanisole: The subsequent regression of the induced lesions in male fischer 344 rat forestomach epithelium

In mice given a single dose of diethylnitrosamine, a hepatonecrotic dose of carbon tetrachloride, 5 weeks after dosing with DEN and repeated 6 times at 4-weekly intervals, augmented the tumour yield in the livers. A single hepatonecrotic dose of CCl4 24 h before a single dose of DEN also increased the number of tumours produced. The effect of the repeated administration of CCl4 after the dose of DEN occurred in addition to, and was therefore independent of, the enhancing effect of a single dose of CCl4 before DEN. These results may be interpreted as implying (1) that the liver in the regenerative phase after a hepatonecrotic dose of CCl4 is more susceptible to an initiating action of DEN, i.e. produces more potential foci of tumour growth than in the normal liver and (2) that the repeated doses of CCl4 leading to repeated phases of regeneration, after the dose of DEN, provide a promoting stimulus.

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