Fine structural changes induced in rat hepatocytes by single doses of 3'-methyl-4-dimethylaminoazobenzene

Acute and persistent ultrastructural changes in rat liver after a single dose of 2‐acetylaminofluorene: Effect of co‐administration of cycloheximide

“…This enhancing effect of CHM-protection was most conspicuous after 24 weeks, when these alterations were considerably more developed in the rats which had originally received both agents. There is a striking parallel between these findings and those obtained previously by combined 3'-MeDAB and CHM treatment (Flaks and Teh, 1976) particularly with regard to the granular endoplasmic reticulum. Disorganisation of the granular endoplasmic reticulum by acute exposure to carcinogenic aminofluorenes has been reported by other workers (Glazer and La Via, 1975;Gustaffson and Afzelius, 1963), although its persistence after such treatment has not been documented before now.…”

“…The only changes in hepatic cell fine structure induced by CHM, as previously described (Flaks and Teh, 1976;Verbin et al, 1969) are loss of glycogen, moderate hypertrophy of the agranular endoplasmic reticulum in the former glycogen areas and a slight decrease in the amount of granular endoplasmic reticulum. The morphology of the latter organelle remains essentially unaltered, although the individual cisternal arrays appear to be smaller than those of normal rat hepatocytes.…”

“…It is thus conceivable that an initial alteration in the structure of the granular endoplasmic reticulum could become persistent if it resulted in the production of abnormal membranes (Flaks, 1970). Such a mechanism might account for the persistence of alterations in this organelle observed in the present study, as well as after a single dose of 3'-MeDAB (Flaks and Teh, 1976) and following chronic treatment with 2-AAF. The epigenetic theory of carcinogenesis propounded by Pitot, and based on biochemical evidence, suggested that a persistent change in the membranes of the granular endoplasmic reticulum may be the primary event in the induction of neoplasia (Pitot, 1969;Pitot et al, 1965;Pitot and Heidelberger, 1963).…”

“…Electron microscopy has shown that this procedure prevents the development of a toxic cytoplasmic hepatocellular lesion following acute exposure to DL-ethionine or 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) Teh, 1975, 1976) without preventing the appearance of other morphological alterations, particularly of the granular endoplasmic reticulum, which are similar to those induced during liver carcinogenesis by these agents and also to those observed in hepatic cell neoplasms. It has also been shown that the granular endoplasmic reticulum changes produced by a single dose of 3'-MeDAB in this experimental model, are persistent (Flaks and Teh, 1976). Hitherto there has been no information concerning the ability of a single dose of 2-AAF to induce persistent fine structural hepatic cell changes.…”

“…At this dosage level, CHM specifically inhibits protein synthesis by 90 per cent. (Farber and Farmar, 1973;Lieberman et al, 1970), is non-toxic to the liver (Flaks and Teh, 1976;Verbin et al, 1969Verbin et al, , 1971 and has a well-documented protective effect against acute toxicity in a number of tissues (Farber el al., 1971;Nicoll, 1974, 1975;Teh, 1975. 1976;Lieberman, 1972;Lieberman et a/.. 1970;Longnecker, 1972).…”