Chemical Carcinogenesis: Interactions of Carcinogens with Nucleic Acids

Rajalakshmi, S.; Rao, Prema M.; Sarma, D.S.R.

doi:10.1007/978-1-4615-6598-7_10

Cited by 5 publications

(5 citation statements)

References 393 publications

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“…In general, any given carcinogen will induce a broad spectrum of DNA lesions, as exemplified by y rays and alkylating agents (Cerutti, 1978;Rajalakshmi et al, 1982;Paterson and Gentner, 1984). Gamma rays cause perhaps one hundred or more chemically distinct alterations in the four constitutive bases and sugar moiety of DNA, as well as single-and double-strand breaks with various types of end-groups, and all three kinds of crosslinks.…”

Section: Carcinogens-classes Modes Of Action An11 Types Of Dna Lesimentioning

confidence: 97%

“…living cells, should possess a battery of coordinated enzymatic processes that repair, tolerate, or otherwise circumvent injury to DNA (reviewed in Hanawalt et al, 1979;Lindahl, 1982;Rajalakshmi et al, 1982;Paterson and Gentner, 1984). Three basic systems are reasonably well-defined: direct reversal, excision repair, and postreplication repair.…”

Section: Basic Dna Repair Systems In Human Cellsmentioning

confidence: 99%

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Cancer predisposition, carcinogen hypersensitivity, and aberrant DNA metabolism

et al. 1984

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Section: Carcinogens-classes Modes Of Action An11 Types Of Dna Lesimentioning

confidence: 97%

Section: Basic Dna Repair Systems In Human Cellsmentioning

confidence: 99%

Cancer predisposition, carcinogen hypersensitivity, and aberrant DNA metabolism

et al. 1984

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“…There is evidence that an epoxide arises as an intermediate in the biotransformation of PHB and other barbiturates in the liver (54)(55)(56)(57), and formation of this or other electrophilic metabolites could be enhanced by, or result from, the altered hepatic metabolism of PHB in rats fed a CD diet (58). Thus, in rats fed a CD + PHB diet, generation of such a critical metabolite(s) could be responsible (59) for the inhibition of DNA synthesis and proliferation of noninitiated hepatocytes. On the other hand, initiated hepatocytes could be spared this effect of PHB, because they have an impaired uptake and/or metabolism of xenobiotics (60) or because they have a high activity of epoxide hydrolase (61).…”

Section: Resultsmentioning

confidence: 91%

Endogenous hepatic growth‐modulating factors and effects of a choline‐devoid diet and of phenobarbital on hepatocarcinogenesis in the rat

Lombardi

Ove

Reddy

1985

Nutrition and Cancer

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The activities of an endogenous inhibitor and of a stimulator of cell proliferation were assayed in the livers of sham-operated (SO) or partially hepatectomized (PH) adult rats; rats fed a choline-supplemented (CS) or a choline-devoid (CD) diet; the same diets followed by acute CCl4 intoxication; the same diets supplemented with phenobarbital (PHB); or a CD diet containing DL-ethionine (ETH). The inhibitor and the stimulator were semipurified by fractional ethanol precipitation of a liver cytosolic fraction, and their activities were assessed by means of bioassays in vitro. The livers of SO rats and of rats fed the CS diet contained only inhibitor activity. Following PH, a CD diet, or CCl4 intoxication the inhibitor activity was suppressed, and there was a simultaneous appearance of a stimulator activity. Thus, PH, a CD diet, and CCl4 intoxication cause similar cellular (loss and regeneration) and humoral-homeostatic changes in adult rat livers. We propose that these changes constitute a basic attribute of the mechanism whereby the three conditions affect similarly hepatocarcinogenesis in the rat, especially in the case of a CD diet, because the changes it induces are chronic rather than acute. PHB, another promoter of chemical hepatocarcinogenesis, affected neither the inhibitor nor the stimulator activity. Thus, PHB seems to be acting by a different mechanism than that of the other three agents. ETH did not modify the shift in the balance of the growth-modulating factors induced by a plain CD diet. This shift may account for the marked stimulation of carcinogen-induced oval cell proliferation exerted by a CD diet. The significance of these results is discussed in the context of known effects of a CD diet and of PHB on hepatocarcinogenesis in rats.

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“…It is widely believed that the major target is DNA. As has been repeatedly shown, the DNA targets for carcinogens may be the bases themselves, the phosphate groups, or the three-dimensional structure of DNA (8,9). An impressive literature exists on the many details concerning the specific adducts formed, their reactivity, and possible relevance to the ultimate development of cancer …”

Section: Molecular Targetsmentioning

confidence: 99%

Possible etiologic mechanisms in chemical carcinogenesis.

Farber

1987

Environ Health Perspect

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Some highlights in the development of our knowledge about carcinogens as etiological agents for cancer are reviewed briefly. Advances during the past 20 years relating to metabolic activation with the genesis of reactive metabolites, molecular targets and their interactions with activated carcinogens, oncogenes as molecular targets and the dependence on cell proliferation, all relating to the initiation process, are reviewed. Critical to initiation is the new phenotype in the initiated cell, known only in one instance, the rat liver, in which the characteristic change is one of resistance to many xenobiotic influences. The need for clonal expansion of initiated cells as essential for carcinogenic effects is discussed. Differential inhibition has been shown as a dominant mechanistic pattern in the liver. In other systems, the manner in which clonal expansion is achieved is not evident. The need for studies of the processes involved in carcinogenesis, as well as the agents, is emphasized, in view of the continuing validity of the cell concept as the key to integrating the increasingly large volume of data from the molecular with the biological.

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Chemical Carcinogenesis: Interactions of Carcinogens with Nucleic Acids

Cited by 5 publications

References 393 publications

Cancer predisposition, carcinogen hypersensitivity, and aberrant DNA metabolism

Cancer predisposition, carcinogen hypersensitivity, and aberrant DNA metabolism

Endogenous hepatic growth‐modulating factors and effects of a choline‐devoid diet and of phenobarbital on hepatocarcinogenesis in the rat

Possible etiologic mechanisms in chemical carcinogenesis.

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