The action of aflatoxin B1 on the rat liver

Clifford, Janet I.; Rees, K. R.

doi:10.1042/bj1020065

Cited by 181 publications

(39 citation statements)

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“…It is, therefore, easy to understand the activity of these polysomes in v i m . This hypothesis is in agreement with the results of Clifford et al [4] who also found no differences between biological activity in v i m of polysomes treated with aflatoxin in vivo and control polysomes. However, with liver slices these authors showed a specific inhibition of protein synthesis by aflatoxin-treated polysomes.…”

Section: Biological Activity Of Treated Polysomessupporting

confidence: 93%

Translational Step Inhibited in vivo by Aflatoxin B₁ in Rat‐Liver Polysomes

Sarasin

Moulé

1975

European Journal of Biochemistry

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Aflatoxin B, strongly inhibits protein synthesis in rat liver cells. We previously demonstrated that this inhibition could be divided into two steps: up to 5 h aflatoxin blocks protein synthesis directly and specifically at the polysome level ; beyond 7 h protein synthesis inhibition appears chiefly as a consequence of transcription impairment due to drug action. This paper confirms the foregoing results and represents an attempt to localize the translational step inhibited in vivo by aflatoxin B1. We used the simulation study developed by Li, Kisilevsky, Wasan and Hammond, 1972 (Biochim. Biophys. Actu, 272,451 -462) to determine precisely the site inhibited in vivo after drug intoxication. This analysis is based on two parameters: the kinetics of polysome labeling to follow the nascent peptide synthesis, and the kinetics of supernatant labeling to follow the completed protein synthesis.Up to 5 h after dosing, aflatoxin specifically inhibits the elongation and/or termination steps during protein synthesis ; after longer periods of time inhibition occurs essentially at the initiation step. When the intracellular concentration of aflatoxin is too high, particularly 2 h after dosing, each step of protein synthesis is blocked.Polypeptide synthesis by the postmitochondrial supernatants isolated from aflatoxin-treated animals is impaired in the same proportion as protein synthesis in vivo. The damage caused by aflatoxin is mostly observed on microsomes. However, purified polysomes isolated from aflatoxintreated rats synthesize proteins in vitre to the same extent as those from controls. These results suggest that aflatoxin metabolite(s) are bound to polysomes with noncovalent bonds. These active metabolites are probably lost during polysome isolation procedures.Finally, relationships between protein metabolism and aflatoxin carcinogenesis are discussed.Aflatoxin B1, a highly potent hepatocarcinogen produced by Aspergillus fluvus, strongly impairs liver cell metabolism and more specifically transcriptional and translational processes [l, 21. This pleiotropic action of aflatoxin B, on cell syntheses explains its short-term toxic effects.A single injection of this drug inhibits protein synthesis in vivo within 30 min, the reversibility of this impairment depending on the aflatoxin dose. The studies of the aflatoxin action on protein synthesis both in vivo and in vitro have thus far led to contradictory results 13 -51.We previously showed that at least two steps are observed in the complex alteration of translation following aflatoxin administration : beyond 7 h protein synthesis inhibition appears chiefly as a conseAbbreviation. RNA . protein particles, ribonucleoprotein particles: polysomes + monosomes + ribosomal subunits. quence of transcription impairment that decreases both ribosomal and messenger RNAs; by 24 h total cellular RNA has decreased 50 % [6]. A concomitant disaggregation of polysomes reaches about 55 % 20 h after dosing. Up to 5 h, however, the amount of polysomes in the cell does not decrease significa...

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Section: Biological Activity Of Treated Polysomessupporting

confidence: 93%

Translational Step Inhibited in vivo by Aflatoxin B₁ in Rat‐Liver Polysomes

Sarasin

Moulé

1975

European Journal of Biochemistry

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“…Furthermore, histological studies on the sequential alterations produced by AFB (Butler, 1964) and fluorescence microscopic studies on the cellular localization of this carcinogen (Stora et al, 1979;Stora, 1980) have been reported. However, the AFBinduced liver biochemical changes reported previously were confined to the initial fewv days of the acute injury stage (Shank & Wogan, 1966;Svoboda et al, 1966;Clifford & Rees, 1967). Since available information does not establish the correlation between sequential biochemical and histological changes in rats treated with AFB, we have undertaken an investigation of the sequential effects of the toxin on the biochemical parameters in the serum and the biochemical and histological characters in the liver of rats for a period of 28 days after a single dose.…”

mentioning

confidence: 88%

“…Alterations of serum, inorganic phosphorus, glucose, cholesterol and albumin are shown in Table III (Wogan, 1968(Wogan, , 1969Akinrimisi et al, 1974;Yu, 1977). However, studies of AFB action on protein synthesis and protein content in the rat liver have yielded contradictory results (Clifford & Rees, 1967;Shank & Wogan, 1966;VillaTrevino & Leaver, 1968;Ramachandra Pai et al, 1978). In concerning the effect of AFB on liver protein content, some reported no significant effect (Shank & Wogan, 1966) but Ramachandra Pai et al (1978) showed a significant decrease on Day 1 after dosing.…”

Section: Body Weightmentioning

confidence: 99%

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Sequential biochemical and histological changes in rats treated with aflatoxin B1

Yin¹,

Kao²,

Lee³

1980

Br J Cancer

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Summary.-Thirteen biochemical parameters (viz. glucose, calcium, inorganic phosphorus, urea nitrogen, uric acid, cholesterol, albumin, total protein, total bilirubin, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase) were determined in serum and partly in liver of rats 1-28 days after i.p. aflatoxin B1 (AFB) (3 mg/kg). Histological examinations of the liver were also made in parallel to the biochemical studies. In the serum, enzyme activities and total bilirubin level increased and peaked on the 2nd day, while other parameters showed diverse changes after AFB treatment. On the other hand, activities of aspartate aminotransferase and alanine aminotransferase in the liver significantly decreased and reached a minimum on the 2nd day after AFB administration. The depression of the liver enzyme activities persisted over 7 days. The liver protein content also reduced transiently during 1-1-5 days. However, all biochemical parameters returned to normal levels 2 weeks after treatment, and remained so throughout the rest of experimental period. Histological changes in the liver were very similar to those reported by others.

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“…It inhibits phospholipid synthesis in rat liver (Clifford & Rees, 1967) and labelled acetate incorporation into rat liver cholesterol (Kato, Onoda & Omori, 1969), and phospholipids, cholesterol and neutral fats of human skin (Black, Smith, Austin & Rauschkolb, 1970). It has also been demonstrated (Tung, Donaldson & Hamilton, 1972) that dietary aflatoxin decreases serum triglyceride fatty acids, total phospholipids and cholesterol levels in chickens.…”

Section: Aflatoxinmentioning

confidence: 99%