Changes in the fine structure of rat hepatocytes during the early phases of chronic 2-acetylaminofluorene intoxication

The Effects of Steroid Hormones and Carcinogens on the Interaction of Membranes with Polysomes

“…The importance of this type of interaction in the transformation of tissues in vivo is clearly impossible to evaluate at the present time but such an initial interaction in vivo is certainly consistent with the frequent reports of rough endoplasmic membrane degranulation (Baglio and Farber, 1965;Svoboda and Higginson, 1968;Flaks, 1970) and binding of carcinogens to cytoplasmic and microsomal protein (Miller and Miller, 1952;Wiest and Heidelberger, 1953;Hultin, 1956) …”

Synthesis and secretion of albumin in rats during treatment with a carcinogenic dose of N-2-acetylaminofluorene

“…Such changes are in accord with the results of a morphological study by Flaks (1970). Significantly, the loss of membrane-bound ribosomes is caused by chronic treatment with a wide range of chemical carcinogens (Farber, 1956;Porter & Bruni, 1959;Svoboda & Higginson, 1968;Williams et al, 1973) and indeed is the only common morphological change reported.…”

“…CHRONIC ADMINISTRATION of a number of chemically diverse carcinogens has been shown to decrease the amount of hepatic rough endoplasmic reticulum in vivo (Flaks, 1970;Porter & Bruni, 1959;Williams et al, 1973;Svoboda & Higginson, 1968;Farber, 1956) either by morphological analysis (e.g. after N-2-acetylaminofluorine (N-2-AAF), 3'methyldimethylaminoazobenzene, ethionine or thioacetamide) or by subeellular fractionation and chemical analysis (in the case of aflaxtoxin B1).…”

“…N-2-AAF has been shown to reduce the number of membrane-bound ribosomes in vivo (Flaks, 1970) and in vitro (Palmer et al, 1978), whilst the noncarcinogenic N-4-AAF has no effect in vivo (Flaks, 1972) or in vitro (Williams & Parry, 1975). N-2-AAF is also a carcinogen of relatively low toxicity which causes no detectable gross damage to the nucleolus or the nucleus when administered in a carcinogenic dose (Flaks, 1970) and, finally, a minimum period of exposure to the carcinogen (4 weeks for this regimen of treatment) is needed to initiate an irreversible progression towards neoplasia which takes 5-8 months (Miller et al, 1961 Control rats received 1 ml 7 % Gum Arabic in isotonic saline i.p. each week, whilst treated rats received 10 mg N-2-AAF per week i.p.…”

The Effects of Aflatoxin B1 in vivo on Membrane—Ribosome Association

“…Degranulation and disorganization of the rough surfaced endoplasmic membranes in vivo have been described for carcinogens as diverse as diethyl-and dimethyl-nitrosamines (Svoboda and Higginson, 1968;Magee and Swann, 1969), 2-acetylaminofluorene (Flaks, 1970), aminoazo-dyes (Porter and Bruni, 1959;Ketterer, Holt and RossMansell, 1967), ethionine (Svoboda and Higginson, 1968;Baglio and Farber, 1965), benz[a]pyrene (Harris et al, 1971), tannic acid (Svoboda and Higginson, 1968;Reddy et al, 1970) and aflatoxin B1 (Svoboda and Higginson, 1968;Butler, 1966). The significance of such an effect remains to be evaluated but it is likely to be an early event since most carcinogens require metabolic activation and the enzymes responsible are located mainly in the endoplasmic reticulum.…”