Asbestos, radiation and oncogenic transformation

Hei, Tom K.; Hall, Eric J.; Osmak, R S

doi:10.1038/bjc.1984.241

Cited by 26 publications

(17 citation statements)

References 15 publications

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“…40 However, Hei et al failed to demonstrate the genotoxic activity of paclitaxel in the C3H 10T1/2 mouse embryo fibroblast cell line. 43 The aneugenic effects of paclitaxel can easily be compared to those induced by other tubulin-binding agents such as vinca alkaloids. Different studies demonstrated that vinblastine, [44][45][46] vincristine, 47,48 and vindesine 49 increased the frequency of MNE from the blood.…”

Section: Discussionmentioning

confidence: 99%

Weekly administration of paclitaxel induces long-term aneugenicity in nude mice

Galmarini

Bouchet²,

Falette³

et al. 2007

Cancer Biology & Therapy

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ABBreViAtioNs MNE ACKNowLedGeMeNtsBenjamin Bouchet is a recipient of a "Foundation pour la Recherche Medicale" grant. ABstrACtWe investigated the potential in vivo aneugenic effects associated with paclitaxel treatment. For this purpose, we treated female nude mice with paclitaxel using doses equivalent to those used in weekly schedules at the clinical level (three cycles of 30 mg/kg/week for three consecutive weeks followed by one resting week). We then evaluated the frequencies of micronucleated erythrocytes (MNE) in peripheral blood using the acridine orange micronucleus assay. The frequency of MNE was evaluated after 24 h and 168 h of administration of the last dose of each paclitaxel cycle (STA mice group) as well as after one year of the first dose of treatment (LTA mice group). We also analyzed the cytology of peripheral blood and bone marrows obtained from these mice at each time period. In the STA mice group, three cycles of paclitaxel induced a 2.4-fold increase in MNE frequencies compared to the control group (p < 0.01). This effect was observed after 24 h of the last dose of each chemotherapy cycle and persisted at least for 168 h. In the LTA mice group, paclitaxel-treated mice presented a 1.8-fold increase in the MNE frequency (p = 0.01) indicating that paclitaxel-induced MNE increase lasted for at least one year. Although the appearance of micronuclei in erythrocytes and granulocytes in peripheral blood and bone marrow cytological smears, there was no evidence of myeloproliferative disease. The present data therefore indicate an aneugenic potential of paclitaxel for humans, which should be considered in the risk-benefit analysis of its increasing clinical use.

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Section: Discussionmentioning

confidence: 99%

Weekly administration of paclitaxel induces long-term aneugenicity in nude mice

Galmarini

Bouchet²,

Falette³

et al. 2007

Cancer Biology & Therapy

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“…[20][21][22][23][24] These N-oxides are widely used in the synthesis of various organic compounds and as bioreductive drugs. 25,26 From the literature survey it was found there was no information available on the oxidation of pyrazines brought about by oxidants with regards to the kinetic and mechanistic points of view. Therefore, the mechanism and rate law for this redox system were obscure.…”

Section: Introductionmentioning

confidence: 99%

N-Oxidation of Pyrazines by Bromamine-B in Perchloric Acid Medium: Kinetic and Mechanistic Approach

2009

Bulletin of the Korean Chemical Society

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Kinetic investigations on the oxidation of pyrazine and four 2-substituted pyrazines viz., 2-methylpyrazine, 2-ethylpyrazine, 2-methoxypyrazine and 2-aminopyrazine by bromamine-B (BAB) to the respective N-oxides have been studied in HClO4 medium at 303 K. The reactions show identical kinetics being first-order each in [BAB] . Effect of ionic strength of the medium and addition of benzenesulfonamide or halide ions showed no significant effect on the reaction rate. The dielectric effect is positive. The solvent isotope effect was studied using D2O. The reaction has been studied at different temperatures and activation parameters for the composite reaction have been evaluated from the Arrhenius plots. The reaction showed 1:1 stoichiometry and the oxidation products of pyrazines were characterized as their respective N-oxides. Under comparable experimental conditions, the oxidation rate of pyrazines increased in the order: 2-aminopyrazine > 2-methoxypyrazine > 2-ethylpyrazine > 2-methylpyrazine > pyrazine. The rates correlate with the Hammett σ relationship and the reaction constant ρ was found to be -0.8, indicating that electron donating centres enhance the rate of reaction. An isokinetic temperature of β = 333 K, indicated that the reaction was enthalpy controlled. A mechanism consistent with the experimental results has been proposed in which the rate determining step is the formation of an intermediate complex between the substrate and the diprotonated species of the oxidant. The related rate law in consistent with observed results has been deduced.

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“…Recent studies have shown that asbestos fibres can also potentiate the in vitro oncogenicity of radiation (Hei et al, 1984a). In an attempt to clarify whether such potentiation could be due to chemical contaminants the native fibres may contain, the ability of acid-leached asbestos fibres to influence radiation induced transformation incidence in C3H lOTl/2 cells was investigated.…”

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confidence: 99%

“…The fibre preparation and culture conditions have been described previously (Hei et al, 1984a). Basically, UICC standard reference samples of crocidolite and amosite were weighed out, suspended in distilled water, sterilized by autoclaving and used at the concentrations indicated.…”

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confidence: 99%

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Correlation of in vitro genotoxicity and oncogenicity induced by radiation and asbestos fibres

Hei¹,

Geard²,

Osmak³

et al. 1985

Br J Cancer

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Summary The in vitro cytotoxicity and oncogenic potential of both native and acid leached asbestos fibres were studied using the C3H IOTI/2 cell model. Both native and leached fibres induced a dose-dependent toxicity. At high fibre concentrations, acid leached fibres were significantly less toxic than their untreated counterparts. While asbestos fibres alone do not induce oncogenic transformation at the concentration examined, it was found that both leached and native fibres substantially enhanced the oncogenicity of gamma-irradiation in a more than additive fashion. Although no significant chromosomal aberrations or sister chromatid exchanges (SCE) were found in asbestos treated cultures, a significantly higher number of SCEs was observed in cells treated with both asbestos and radiation compared to cells receiving radiation alone. The results suggest that the enhancement in radiation induced oncogenicity by asbestos fibres may be attributed to the mere physical presence of the fibres rather than any chemical contaminants the fibres may contain. Furthermore, the carcinogenicity of asbestos may be unrelated to genotoxicity.

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Asbestos, radiation and oncogenic transformation

Cited by 26 publications

References 15 publications

Weekly administration of paclitaxel induces long-term aneugenicity in nude mice

Weekly administration of paclitaxel induces long-term aneugenicity in nude mice

N-Oxidation of Pyrazines by Bromamine-B in Perchloric Acid Medium: Kinetic and Mechanistic Approach

Correlation of in vitro genotoxicity and oncogenicity induced by radiation and asbestos fibres

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