This is the first report on cerebral changes in eight patients who died of paraquat poisoning. These included generalized oedema, haemorrhages (both subependymal and subarachnoid), glial reactions (microglial activity and astrocytic response) and meningeal inflammation. Oedema and haemorrhage were the most consistent and significant findings; they suggest that paraquat may damage the cerebral blood vessels. The distribution of haemorrhages was unusual and resembled that seen in thiamine deficiency.
Though much is known about the pathology of the rat’s liver during chemical carcinogenesis, and the associated biochemical changes have been studied extensively with some compounds, especially 4-dimethylaminoazobenzene (DAB, ‘butter yellow’), hardly any attempt has been made to follow such changes progressively or to correlate them with the histological findings. Malignant tumours of the liver are roughly divisible into cancers of the bile duct cells (cholangiocarcinomas) and those of the liver cells (hepatomas). In our experiments cholangiocarcinomas were produced by feeding thioacetamide or DAB, whereas hepatomas resulted if DAB with a vitamin B-rich diet was used. The events which decide the type of tumour which develops may be summarized thus: a cholangiocarcinoma occurs when the following changes are found in the liver, damage to parenchymal cells, proliferation of bile duct tissue, a drop in the mitochondrial fraction, and the phenomenon of ‘ageing’ of mitochondria. During this time there is a gradual fall in the phospholipid synthesis and, finally, the development of the tumour. In contrast, hepatoma results if this precancerous process be slowed down as, for instance, by the addition of B vitamins to the diet. The parenchymal cell damage is then qualitatively similar to that seen in more rapid carcinogenesis, but fewer dying cells can be made out. In such animals the mitochondrial population is not depleted, mitochondria do not exhibit ‘ageing’ and phospholipid synthesis is unaltered until the onset of the hepatoma.
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