Transformation of Syrian Hamster Embryo Cells by Diverse Chemicals and Correlation with Their Reported Carcinogenic and Mutagenic Activities

Pienta, Roman J.

doi:10.1007/978-1-4613-3072-1_7

Cited by 61 publications

(14 citation statements)

References 36 publications

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“…We isolated SHE fibroblasts from 13-day-old embryos and grew the cells in a humidified atmosphere with 12% CO 2 at 37°C. The culture medium was modified Dulbecco's Eagle's reinforced medium (Gibco, Karlsruhe, Germany), supplemented with 15% fetal calf serum (Flow Laboratories, Meckenheim, Germany), NaHCO 3 (7.5%), 1% glucose, 10,000 IU penicillin, and 10 mg/mL streptomycin according to the standard procedure described by Pienta (22).…”

Section: Methodsmentioning

confidence: 99%

Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts.

Rahman

Lohani

Dopp

et al. 2002

Environ Health Perspect

355

218

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Inhaled ultrafine titanium dioxide (UF-TiO2) particles cause pronounced pulmonary inflammation, in contrast to fine TiO2. Previous studies provide evidence for the production of reactive oxygen species by alveolar macrophages, after overloading with UF-TiO2 particles and cytotoxicity of UF-TiO2 in rat lung alveolar macrophages. UF-TiO2 also causes pulmonary fibrosis and lung tumors in rats. UF-TiO2 particles are photogenotoxic, but in general, information on the genotoxicity of UF-TiO2 is still limited. We studied the potential of UF-TiO2 (particle size less than or equal to 20 nm) and fine TiO2 (particle size > 200 nm) to induce chromosomal changes, which can be monitored by the formation of micronuclei (MN) in Syrian hamster embryo (SHE) cells. We also analyzed UF-TiO2-treated cells for apoptosis induction. The MN assay revealed a significant increase in MN induction (p less than or equal to 0.05) in SHE cells after treatment with UF-TiO2 (1.0 micro g/cm2) for 12 hr (mean, 24.5 MN/1,000 cells), 24 hr (mean, 31.13 MN/1,000 cells), 48 hr (mean, 30.8 MN/1,000 cells), 66 hr (mean, 31.2 MN/1,000 cells), and 72 hr (mean, 31.3 MN/1,000 cells). Bisbenzimide staining of the fixed cells revealed typical apoptotic structures (apoptotic bodies), and the apoptosis-specific "DNA ladder pattern" resulting from internucleosomal cleavage was identified by gel electrophoresis. Furthermore, transmission electron microscopy of the exposed cells revealed the typical chromatin compaction of apoptosis.

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Section: Methodsmentioning

confidence: 99%

Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts.

Rahman

Lohani

Dopp

et al. 2002

Environ Health Perspect

355

218

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“…Following a 48-h incubation period in a humidified incubator at 12% co2 and 37°C, the medium was removed, the cells were washed with PBS and supplied with fresh culture medium. Eight days later, the cells were fixed with methanol, stained with 10% aqueous Giemsa and scored for cloning efficiency and morphological transformation according to the criteria (altered colony morphology consisting of criss-crossing and piling up of cells) described previously in detail by Herwald and Sachs (1965), DiPaolo et al (1971) and Pienta (1980). Cell survival was determined in parallel by the conventional colony assay.…”

Section: In Uitro Iransformation Assaymentioning

confidence: 99%

5-Azacytidine induces micronuclei in and morphological transformation of Syrian hamster embryo fibroblasts in the absence of unscheduled DNA synthesis

Stopper

Pechan

Schiffmann

1992

Mutation Research Letters

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Summary lt is known that 5-azacytidine (5-AC) induces tumors in several organs of rats and mice. The mechanisms of these effects are still poorly understood although it is known that 5-AC can be incorporated into DNA. Furthermore, it can inhibit DNA methylation. The known data on its clastogenic andjor gene mutation-inducing potential are still controversial. Therefore, we have investigated the kinds of genotoxic effects caused by 5-AC in Syrian hamster embryo (SHE) fibroblasts. Three different endp6ints (micronucleus formation, unscheduled DNA synthesis (UDS) and cell transforrnation) were assayed under similar conditions of metabolism and dose at target in this cell system. 5-AC induces morphological transformation of SHE cells, but not UDS. Therefore, 5-AC does not seem to cause repairable DNA lesions. Furthermore, our studies revealed that 5-AC is a potent inducer of mkronuclei in the SHE system. Immunocytochemical analysis revealed that a certain percentage of these contain kinetochores indicating that 5-AC may induce both clastogenic events and numerical chromosome changes.5-Azacytidine (5-AC) is an effective antineoplastic compound which has been used in the treatment of leukemia (Saiki et al., 1978). lt induces tumors in several organs of rats (Carr et al., 1984) and mice in utero (Schmahl et al., 1985). 5-AC is a cytidine analog containing a nitrogen atom at the 5 position instead of a carbon. Incor-

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Section: Morphological and Neoplastic Transformation In Vitro By Estrmentioning

confidence: 99%

“…MN packing acentric chromosomal fragments appear to be induced by clastogens, while MN enclosing whole chromosomes are induced by agents that affect the mitotic apparatus. The majority of DES-induced and E2-induced MN contains whole chromosomes, which are demonstrated both with antikinetochore antibodies and with the centromerespecific DNA probe (67 (64), which have both oxidative (28) and peroxidative activities (29). Schnitzler et al (67) have shown that the mechanism of DES-induced MN is different from that of E2-induced MN using SHE cells and ovine seminal cells.…”

Section: Morphological and Neoplastic Transformation In Vitro By Estrmentioning

confidence: 99%

“…Thus, estrogenic activity of the compounds can be excluded in this in vitro assay. The cells do, however, have the ability to metabolize estrogens (28,29), and the role of metabolic activation in the carcinogenesis activity of estrogens in this model is under investigation as discussed later.The role of mutagenesis in the neoplastic transformation of SHE cells by estrogens has been studied extensively. We have demonstrated that treatment of SHE cells with DES or E2 induces cell transformation without measurable gene mutations, unscheduled DNA synthesis (UDS) or structural chromosome aberrations (19,20,23 …”

mentioning

confidence: 99%

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Neoplastic transformation of cultured mammalian cells by estrogens and estrogenlike chemicals.

Tsutsui

Barrett

1997

Environ Health Perspect

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Estrogen use has been associated with an increased risk for breast cancer and endometrial cancers in women (1-4). Various natural and synthetic estrogens also induce mammary, pituitary, cervical, uterine, and renal tumors in rodents (4-5). Diethylstilbestrol (DES), a synthetic estrogen, is well known to be carcinogenic to humans (6). The cellular and molecular mechanism(s) whereby estrogen-induced neoplastic events occur have not been fully elucidated, but there is strong evidence that estrogens are epigenetic carcinogens, acting via a promoting effect related to cellular proliferation, mediated through the estrogen receptor (7-15). However, it has been shown that estrogenic activity is not sufficient to explain the carcinogenic activity in vivo and in vitro under certain experimental conditions. Another mechanism, related to mutagenic changes, has been suggested in studies of estrogen-induced carcinogenesis (16)(17)(18)(19)(20)(21)(22)(23)(24) into the cellular and molecular mechanisms of carcinogenesis, which is difficult in whole-animal or human systems. We have used Syrian hamster embryo (SHE) fibroblast cell cultures as a model system to study the ability of estrogens to directly transform cells. Morphological and Neoplastic Transformation in Vitro by Estrogens and Estrogenlike ChemicalsMorphological and neoplastic transformation of SHE cells is induced by DES, 17,-estradiol (E2) and other estrogens. We observed that DES and E2 induce transformation of hamster cells that is indistinguishable from that induced by other chemical carcinogens such as benzo [a]pyrene (19,25). Sarcomas are also induced in Syrian hamsters in vivo following subcutaneous injection of DES (26). SHE cells do not express measurable levels of estrogen receptor and estrogen treatment is not mitogenic to the cells (27). Thus, estrogenic activity of the compounds can be excluded in this in vitro assay. The cells do, however, have the ability to metabolize estrogens (28,29), and the role of metabolic activation in the carcinogenesis activity of estrogens in this model is under investigation as discussed later.The role of mutagenesis in the neoplastic transformation of SHE cells by estrogens has been studied extensively. We have demonstrated that treatment of SHE cells with DES or E2 induces cell transformation without measurable gene mutations, unscheduled DNA synthesis (UDS) or structural chromosome aberrations (19,20,23

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Transformation of Syrian Hamster Embryo Cells by Diverse Chemicals and Correlation with Their Reported Carcinogenic and Mutagenic Activities

Cited by 61 publications

References 36 publications

Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts.

Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts.

5-Azacytidine induces micronuclei in and morphological transformation of Syrian hamster embryo fibroblasts in the absence of unscheduled DNA synthesis

Neoplastic transformation of cultured mammalian cells by estrogens and estrogenlike chemicals.

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