Characterization of sheep seminal vesicle cells—a new tool for studying genotoxic effects in vitro

Foth, J.; Schnitzler, Robert; Jager, M. J.; Koob, Michael D.; Metzler, Manfred; Degen, Gisela H.

doi:10.1016/0887-2333(92)90035-p

Cited by 8 publications

(2 citation statements)

References 15 publications

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“…Studies with known clastogens and aneugens in other cell models also provide similar results. For example, when diethylstilbestrol (DES, an aneugen) [32] and 4-nitroquinoline-N-oxide (4-NQO, a clastogen) [32] were both tested for induction of micronuclei in primary cultures of fibroblasts derived from ram seminal vesicles (whose doubling time is about 16 h), it was observed that 4-NQO and DES showed maximal micronuclei induction after 24 h and 12 h of recovery, respectively [33]. Similar results with these two mutagens in primary cultures of Syrian hamster embryo and ovine seminal vesicle cells were also obtained [32].…”

Section: Discussionmentioning

confidence: 99%

Role of exposure/recovery schedule in micronuclei induction by several promutagens in V79-derived cells expressing human CYP2E1 and SULT1A1

Jia

Zhang

Glatt

et al. 2016

Mutation Research/Genetic Toxicology and Environmental Mutagene

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The standard procedure for the micronucleus test in cell lines requires a short exposure (≤0.5 cell cycle) to the test compounds followed by a long recovery (≥1.5 cell cycle), and in case of negative or equivocal results, a second test with extended exposure (≥2 cell cycles) without or with a recovery time. In general the two procedures are advantageous for detecting clastogens and aneugens, respectively. However, whether the recommended procedures apply to micronucleus tests with promutagens in cell lines genetically engineered for expressing biotransformation enzymes has not been identified. In this study, several promutagens dependent on cytochrome P450 (CYP) 2E1 and/or sulfotransferase (SULT) 1A1 were used in the micronucleus test in a Chinese hamster V79-derived cell line expressing human CYP2E1 and SULT1A1 (V79-hCYP2E1-hSULT1A1), with varying exposure/recovery schedules: 3h/21h, 6h/18h, 12h/12h, 18h/6h, and 24h/0h, in comparison with known clastogens and aneugens in V79 control cells. The results showed peaked micronuclei induction by mitomycin C and bleomycin (clastogens) at the 12h/12h schedule, while colchicine and vinblastine (aneugens) showed the strongest effect at 24h/0h. Catechol and trihydroxybenzene (activated by CYP2E1) induced micronuclei most strongly at 6h/18h, whereas somewhat longer exposures were optimal for hydroquinone, another compound activated by CYP2E1. 1-Hydroxymethylpyrene (activated by SULT1A1) and 1-methylpyrene (activated sequentially by CYP2E1 and SULT1A1) produced the highest response with the 18h/6h treatment regimen. Moreover, mitotic arrest by 1-hydroxymethylpyrene was observed in V79-hCYP2E1-hSULT1A1 cells but not in V79 cells, and 1-methylpyrene arrested mitosis in V79-hCYP2E1-hSULT1A1 more strongly than in V79 cells. Our study suggests that intracellular bioactivation of promutagens may not delay the induction of micronuclei in the present model, and 1-methylpyrene and 1-hydroxymethylpyrene may be activated to mitosis-arresting metabolites.

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Section: Discussionmentioning

confidence: 99%

Role of exposure/recovery schedule in micronuclei induction by several promutagens in V79-derived cells expressing human CYP2E1 and SULT1A1

Jia

Zhang

Glatt

et al. 2016

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…E2 exhibits microtubule-disrupting activity both in estrogen receptor-positive and receptor-negative human breast cancer cell lines (51). The disrupting activity is demonstrated also in V79 cells (51,52), which have little capability of metabolizing xenobiotics (56) (63)(64)(65)(66)(67). MN enclose acentric chromosome fragments or whole chromosomes that do not become incorporated into the main nuclei after cell division.…”

Section: Morphological and Neoplastic Transformation In Vitro By Estrmentioning

confidence: 99%

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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Induction of micronuclei by stilbene-type and steroidal estrogens in Syrian hamster embryo and ovine seminal vesicle cells in vitro

Schnitzler

Foth

Degen

et al. 1994

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Characterization of sheep seminal vesicle cells—a new tool for studying genotoxic effects in vitro

Cited by 8 publications

References 15 publications

Role of exposure/recovery schedule in micronuclei induction by several promutagens in V79-derived cells expressing human CYP2E1 and SULT1A1

Role of exposure/recovery schedule in micronuclei induction by several promutagens in V79-derived cells expressing human CYP2E1 and SULT1A1

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

Induction of micronuclei by stilbene-type and steroidal estrogens in Syrian hamster embryo and ovine seminal vesicle cells in vitro

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