Ethionine Carcinogenesis

Farber, Emmanuel

doi:10.1016/s0065-230x(08)60986-0

Cited by 284 publications

(81 citation statements)

References 200 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The molecular basis for the nucleolar fragmentation seems to be most probably related to the induction of an ATP deficiency by ethionine. This analogue of methionine is known to have at least four major metabolic properties, all closely related to methionine (18,19). (18,20).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Disorganization of Hepatic Cell Nucleoli Induced by Ethionine and Its Reversal by Adenine

Shinozuka

Goldblatt

Farber

1968

The Journal of Cell Biology

Self Cite

View full text Add to dashboard Cite

The structure of nuclei and nucleoli of hepatic cells after short-term ethionine administration was investigated with the electron microscope. By 112 hr after the injection, a distinct alteration occurred in the nucleoli which was characterized by the appearance of electronopaque masses in the nucleolonema. After 6-8 hr, the nucleoli showed partial fragmentation into small, dense masses. Large aggregates of interchromatinic granules appeared in the nucleoplasm. Condensation of chromatin became prominent in the nucleoplasm particularly along the nuclear membrane. By 12 hr almost complete fragmentation of nucleoli had occurred. The administration of adenine or methionine at 4 hr prevented the development of nucleolar changes. Also, adenine administration at 8 hr after ethionine completely reversed the nucleolar lesion by 12 hr. After methionine administration at 8 hr, many nucleoli showed incomplete reconstruction with many twisted ropelike structures when viewed 4 hr later. Identical structures were found when adenine was given at 8 hr, and animals were sacrificed 2 hr later. On the basis of this observation, the simplified structures of nucleoli found 2 hr after adenine or 4 hr after methionine appeared to be precursors of the nucleolonema. It is suggested that nucleoli show at least two basic reaction patterns to inhibitors of RNA synthesis, one typified by actinomycin D and one by ethionine.

show abstract

Section: Discussionmentioning

confidence: 99%

“…This analogue of methionine is known to have at least four major metabolic properties, all closely related to methionine (18,19). (18,20). In addition mechanisms (a) and (b) are not rapidly reversed by the administration of methionine.…”

Section: Discussionmentioning

confidence: 99%

The Disorganization of Hepatic Cell Nucleoli Induced by Ethionine and Its Reversal by Adenine

Shinozuka

Goldblatt

Farber

1968

The Journal of Cell Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Figure 1 (Stekol, 1963), and yet gives rise to numerous hepatocarcinomas when included in the diet (Farber, 1963). Although significant transfer of the ethyl group of ethionine to RNA occurs (Farber & Magee, 1960;Craddock, 1969), very little reaction with DNA is observed (Swann et al, 1971;Ortwerth & Novelli, 1969).…”

Section: Enzymatic Methylation In Gene Expressionmentioning

confidence: 99%

“…Since the replicative index of liver is very low, the model suggests that ethionine would be carcinogenic only at high concentration capable of inhibiting DNA methylase over extended periods. Such are the requirements for the induction of hepatic tumours by ethionine (Farber, 1963).…”

Section: Enzymatic Methylation In Gene Expressionmentioning

confidence: 99%

5-Methylcytosine depletion during tumour development: An extension of the miscoding concept

Nyce¹,

Weinhouse²,

Magee³

1983

Br J Cancer

View full text Add to dashboard Cite

Perhaps the most ubiquitous aspect of tumours and the neoplastic cells of which they are composed is their loss of the ability to control cellular functions in a normal way. During the development of the malignant state, the neoplastic cell becomes increasingly refractory to both the internal and external stimulae which integrate its normal counterparts into functional tissues and organ systems. This lack of integration is associated with alterations in the expression of a host of gene products, including, for example, the ectopic biosynthesis of hormones (

show abstract

“…Ethionine is an analogue of methionine and its carcinogenic activity is restricted to liver tissue (Farber, 1963). It can be metabolized in liver to replace the normal amino acid in S-adenosyl methionine.…”

Section: Effects Of Ethionine Promotors and Bromodeoxyuridinementioning

confidence: 99%

A new theory of carcinogenesis

Holliday¹

1979

Br J Cancer

192

View full text Add to dashboard Cite

Summary.-Although many carcinogens are mutagens, there is no direct evidence that the cancer-cell phenotype is the result of gene mutation. Transplantation experiments have strongly indicated that malignant cells can arise or revert to the normal phenotype in the absence of mutation. It is suggested that damage to DNA followed by repair triggers the epigenetic changes in gene expression which are responsible for malignancy. We previously proposed that methylation of specific DNA sequences adjacent to structural genes determines whether or not transcription will occur. Specific methylases are required for the switching on of genes and for the stable maintenance of the methylated state, which provides a basis for the control of gene expression in differentiated cells. It is now seen that damage to DNA followed by repair, just before or just after DNA replication, can lead to the loss of methyl groups. This can induce a switch in gene activity which is heritable, but potentially reversible. The known large difference in the probability of malignant transformation in cells of rodents and large mammals is hard to explain if mutation is responsible. On the other hand, this new theory provides an explanation for this difference, since the probability of epigenetic changes in gene activity will depend on the activity of methylating enzymes and the rate of excision repair. The theory is supported by the evidence that excision repair is more efficient in cultured fibroblasts from large long-lived animals than from small short-lived ones.

show abstract

Ethionine Carcinogenesis

Cited by 284 publications

References 200 publications

The Disorganization of Hepatic Cell Nucleoli Induced by Ethionine and Its Reversal by Adenine

The Disorganization of Hepatic Cell Nucleoli Induced by Ethionine and Its Reversal by Adenine

5-Methylcytosine depletion during tumour development: An extension of the miscoding concept

A new theory of carcinogenesis

Contact Info

Product

Resources

About