Studies on the interactions of dieldrin with mammalian liver cells at the subcellular level

Wright, A. N.; Akintonwa, Dunstan A.A.; Wooder, M.F.

doi:10.1016/0147-6513(77)90013-6

Cited by 32 publications

(10 citation statements)

References 12 publications

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“…A reasonably good correlation between RER degranulation and the carcinogenicity of a series of compounds has been demonstrated (33). Compounds that bring about the detachment of ribosomes (degranulation) of the rough endoplasmic reticulum (RER).…”

Section: Functional Criteriamentioning

confidence: 99%

General Principles for the Prediction of Potential Carcinogenic Activity of Chemical Compounds

Ehrlich¹,

Buu-Hoi²

1988

Natural, Metal, Fiber, and Macromolecular Carcinogens

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Section: Functional Criteriamentioning

confidence: 99%

General Principles for the Prediction of Potential Carcinogenic Activity of Chemical Compounds

Ehrlich¹,

Buu-Hoi²

1988

Natural, Metal, Fiber, and Macromolecular Carcinogens

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“…Although very small amounts of an unidentified biotransformation product were associated with DNA there was no correlation between the extent of binding and susceptibility to tumour formation. It has also been demonstrated that acute exposure to very high doses of dieldrin does not cause DNA strand-breakage in the livers of rats and mice (2).…”

Section: Introductionmentioning

confidence: 99%

“…Oral exposure of CF-1 mice to dieldrin results in a sustained induction of liver microsomal enzyme systems and liver enlargement associated with cellular hypertrophy and increases in total liver DNA (1)(2)(3). These effects have been found to be reversible upon cessation of dieldrin treatment (1,2)..…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, dieldrin and its metabolites gave entirely negative results when evaluated for mutagenic activity in a variety of test systems, including the coupled liver-microsome-bacterial test system employing the liver microsomes from rats and mice (14,15). Studies have also been conducted on the binding of radioactivity to the liver cell DNA of rats and mice after exposure to [ 14 C]dieldrin in vivo (2). Although very small amounts of an unidentified biotransformation product were associated with DNA there was no correlation between the extent of binding and susceptibility to tumour formation.…”

Section: Introductionmentioning

confidence: 99%

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Dose-response analysis of the enhancement of liver tumour formation in CF-1 mice by dieldrin

Tennekes¹,

Edler

Kunz³

1982

Carcinogenesis

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The current study was undertaken to investigate the dose-response characteristics of dieldrin-mediated enhancement of liver tumour formation in CF-1 mice. The median time to tumour development was established in controls, and in dieldrin-treated animals at six levels of continuous exposure (0.1, 1, 2.5, 5, 10 and 20 p.p.m.). The results of the analysis, which was based on liver tumour data from two parallel chronic feeding studies involving 1800 mice, are at variance with those reported by Druckrey for various established chemical carcinogens. In a double-logarithmic system of coordinates there was no linear relationship between the median total dose or the median time to tumour formation and the daily dieldrin exposure level. These results suggest that the tumourigenicity of this compound in CF-1 mouse liver is determined not by the sum of all consecutive doses, but rather by the level of daily exposure, and, presumably, the duration of treatment. This concept is consistent with the observed dose-dependency and reversible nature of dieldrin-induced subcellular changes in mouse liver. These considerations, together with evidence that dieldrin and its mammalian metabolites possess neither genotoxic activity nor potential, are not inconsistent with the concept that this compound is devoid of initiating potential, and operates by enhancing the effect of a genetically linked oncogenic factor in CF-1 mouse liver.

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“…Continuous treatment with microsomal enzyme inducers, such as drugs, food additives and pesticides, results in an induction of liver microsomal enzyme systems, liver enlargement and an in increase in total liver DNA in the initial phases of treatment (Wright et al, 1972(Wright et al, ,1977Tennekes et al, 1981). Thereafter a 'steady-state' situation is maintained, in which the aforementioned remain on a plateau level (i.e., no further increases or decreases of the parameters occur).…”

mentioning

confidence: 96%

Quantitative aspects of accelerated nuclear polyploidization and tumour formation in dieldrin treated CF-1 mouse liver

Ravenzwaay

Kunz²

1988

Br J Cancer

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Summary Nuclear polyploidization in the livers of CF-I mice, exposed to dieldrin (0, 1, 5 and lOppm in the diet), was studied up to the median time of liver tumour development (ranging from 15 to 27 months) in the respective treatment groups. In untreated controls nuclear polyploidization is characterized by a linear increase of octaploid nuclei with age. Approximately 4 months before tumour development a reduction in the tetraploid to diploid ratio is observed. Dieldrin treatment was found to enhance nuclear polyploidization in the initial phases of treatment, as expressed by a dose-dependent increase in octaploid nuclei. In 'steady-state' situations all age dependent changes in the level of polyploidization found in controls were also found in dieldrin treated mice. However, these changes occurred at an increasingly earlier age with higher dieldrin treatment levels. The decrease in the tetraploid:diploid ratio always takes place a few months before tumour development. This change in the ploidy level may thus be related to the subsequent liver tumour formation. The liver tumours themselves appear to originate from a diploid stem line, and were found to increase their degree of polyploidization during growth, eventually developing aneuploid nuclei. A comparison of nuclear polyploidization and liver tumour formation in CF-1 mouse liver for the given dietary dieldrin concentrations showed that liver tumour formation was associated with a constant level of polyploidization. Since polyploidization is an age-dependent process, these findings suggest that liver tumour formation is imminent at a constant biological age and that dieldrin may advance the biological age of CF-I mouse liver.The CF-l mouse strain is characterized by the development of 'spontaneous' liver tumours when they reach an advanced age. Continuous treatment with microsomal enzyme inducers, such as drugs, food additives and pesticides, results in an induction of liver microsomal enzyme systems, liver enlargement and an in increase in total liver DNA in the initial phases of treatment (Wright et al., 1972(Wright et al., ,1977Tennekes et al., 1981). Thereafter a 'steady-state' situation is maintained, in which the aforementioned remain on a plateau level (i.e., no further increases or decreases of the parameters occur). The induced changes are reversible upon withdrawal and elimination of the compound and are not accompanied by evidence of liver damage. Thus, these changes are likely to be an adaptation of the liver to increased functional demands. However, exposure to microsomal enzyme inducers, such as dieldrin has been shown to enhance liver tumour formation in these mice (Walker et al., 1973; Tennekes et al., 1985).Microsomal enzyme inducers are also known to enhance nuclear polyploidization in rodent liver (Bohm & Noltemeyer, 1981). In a recent study (van Ravenzwaay et al., 1987) it was reported that nuclear polyploidization in livers of CF-I mice increased proportionally to the dietary dieldrin concentration within a few weeks after the initiati...

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Studies on the interactions of dieldrin with mammalian liver cells at the subcellular level

Cited by 32 publications

References 12 publications

General Principles for the Prediction of Potential Carcinogenic Activity of Chemical Compounds

General Principles for the Prediction of Potential Carcinogenic Activity of Chemical Compounds

Dose-response analysis of the enhancement of liver tumour formation in CF-1 mice by dieldrin

Quantitative aspects of accelerated nuclear polyploidization and tumour formation in dieldrin treated CF-1 mouse liver

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