Possible two‐stage transplacental liver carcinogenesis in c57bl/6 mice

Armuth, Vlasta; Berenblum, I.

doi:10.1002/ijc.2910200218

Cited by 16 publications

(3 citation statements)

References 5 publications

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“…This hypothesis is derived from multiple lines of thought. For instance, two carcinogens, applied in sequence, are often more successful at initiating cancer in experimental animals than application of a single carcinogen during the same time [1, 2]. Another line of evidence comes from epidemiological observations of a linear correlation between the rate of cancer death and the patients age [3, 4].…”

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confidence: 99%

Wnt and Kras signaling-dark siblings in lung cancer

Pacheco-Pinedo¹,

Morrisey²

2011

Oncotarget

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Aberrant Kras signaling is observed in a high percentage of human lung cancers while activating mutations in the Wnt/β-catenin signaling pathway are only rarely found. Our recent work has shown that the combined activation of both Kras and Wnt/β-catenin signaling leads to a dramatic increase in both tumor incidence and size. Moreover, lung tumors generated by the combined activation of both of these pathways exhibit a distinct phenotype similar to embryonic progenitors found in the developing lung. Thus, combinatorial activation of Kras and Wnt/β-catenin pathways leads to a significant increase in lung tumor formation characterized by a more progenitor like phenotype.

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confidence: 99%

Wnt and Kras signaling-dark siblings in lung cancer

Pacheco-Pinedo¹,

Morrisey²

2011

Oncotarget

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“…Some members of this class also exhibit reproductive toxicity. For example, 2-AAF has been shown to be a teratogen [l-51 and transplacental carcinogen [6,7] in different laboratory animal species. The results of several in vitro studies have established that prior metabolism of parent chemical and damage to DNA are required to observe teratogenicity.…”

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confidence: 99%

2‐aminofluorene bioactivation by human term placental peroxidase

Murthy

Joseph

Kulkarni

1995

Teratog Carcinog Mutagen

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Earlier investigations from our laboratory demonstrated that human term placental peroxidase (HTPP) is capable of metabolism of xenobiotics and endogenous compounds. In this study, purified HTPP was found to bioactivate 2-aminofluorene (2-AF) in the presence of H2O2. 2-AF oxidation was studied spectrophotometrically while radiometry was employed to assess the bioactivation. The rate of oxidation and covalent binding to protein and DNA was dependent upon the pH of the reaction medium and the concentration of 2-AF, the enzyme, and H2O2. To observe maximal enzyme velocity of oxidation, the presence of 16.5 microM H2O2, 100 microM 2-AF, 37 micrograms of the enzyme protein/ml, and pH 7.2 was required. Under optimal assay conditions, the range of specific activity between 130 and 165 nmol of 2-AF oxidized/min/mg HTPP was observed. Using similar assay conditions, the magnitude of covalent binding of [3H]-2-AF to protein (BSA) and calf thymus DNA was found to be about 508 pmol bound/min/mg HTPP/mg BSA and 84 pmol bound/min/mg HTPP/mg DNA, respectively. Potassium cyanide and sodium azide, the known inhibitors of different peroxidases, significantly blocked both the oxidation and covalent binding of 2-AF in a dose dependent manner. These results strongly suggest that peroxidase may be one of the important pathways responsible for the bioactivation of arylamines in human term placenta.

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“…The soft ,8particles of radioactive thymidine possess a short range of radiation. On the assumption that the process of initiating action is mutational and involves the genetic material in the cell nucleus (Barrett et al, 1978), the use of [3H]thymidine should, in theory, serve as an ideal, all-purpose, broad-spectrum initiator for transplacental twostage carcinogenesis.…”

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Tritiated thymidine as a broad spectrum initiator in transplacental two‐stage carcinogenesis, with phorbol as promoter

Armuth

Berenblum

1979

Intl Journal of Cancer

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A single subcutaneous injection of 200 mu Ci [3H] thymidine into pregnant BALD/c mice, followed by intraperitoneal injections of phorbol, twice weekly for 25 weeks, in the offspring, resulted in higher tumour development in the lungs and livers of male and, to a lesser extent, of female offspring, than in their untreated littermates. The difference in overall tumour incidence was statistically significant, but the increases of the individual tumour types were only of borderline significance. Slight carcinogenic activity of [3H]thymidine alone was observed in the mothers, and in the offspring, without phorbol treatment. The results suggest the possibility of using [3H]thymidine as a broad spectrum initiator for transplacental two-stage carcinogenicity studies to determine the organ specificity of different promoting agents.

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Possible two‐stage transplacental liver carcinogenesis in c57bl/6 mice

Cited by 16 publications

References 5 publications

Wnt and Kras signaling-dark siblings in lung cancer

Wnt and Kras signaling-dark siblings in lung cancer

2‐aminofluorene bioactivation by human term placental peroxidase

Tritiated thymidine as a broad spectrum initiator in transplacental two‐stage carcinogenesis, with phorbol as promoter

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