Vincristine sulfate-induced cell transformation, mitotic inhibition and aneuploidy in cultured Syrian hamster embryo cells

Journal Article · Wed Jan 01 04:00:00 EST 1986 · Carcinogenesis; (United States)

DOI:https://doi.org/10.1093/carcin/7.1.131· OSTI ID:5631989

Tsutsui, T; Suzuki, N; Maizumi, H; Barrett, J C

Vincristine, a naturally occurring Vinca alkaloid and widely used anti-neoplastic agent, was examined for its ability to induce cell transformation, inhibition of growth and mitosis, and genetic effects in Syrian hamster embryo cells in culture. Treatment of the cells with doses of less than or equal to 1 ng/ml vincristine sulfate (VCR) had no effect on cell growth, while exposure to greater than or equal to 3 ng/ml reduced the growth rate and treatment with 30 ng/ml resulted in no detectable increase in cell number. At this latter dose the mitotic index of the cells increased significantly suggesting that VCR delayed completion of mitosis. Exposure of the cells to VCR at doses of 1-10 ng/ml for 48 h resulted in morphological transformation of the cells in a doserelated fashion. The vincristine-treated transformed colonies were morphologically indistinguishable from colonies transformed by benzo(a)pyrene or other chemical carcinogens. Morphological transformation was induced by VCR at non-toxic and slightly toxic doses as measured by a reduction in colony-forming ability of the treated cells. Over the dose range which resulted in cell transformation, VCR failed to induce either detectable gene mutations at two genetic loci, unscheduled DNA synthesis, or chromosome aberrations in the Syrian hamster embryo cells. However, a significant dose-dependent increase in aneuploid cells with a near-diploid chromosome number was induced by VCR. Both chromosome losses and gains were induced which is consistent with a non-disjunctional mechanism. These results further support our hypothesis that aneuploidy is one possible mechanism for induction of this early step in the neoplastic transformation of Syrian hamster embryo cells. Furthermore, these findings indicate that VCR may have some carcinogenic potential if exposure to rapidly dividing cells occurs.

• Research Organization: Nippon Dental Univ. Tokyo, Japan
• OSTI ID: 5631989
• Journal Information: Carcinogenesis; (United States), Journal Name: Carcinogenesis; (United States) Vol. 1; ISSN CRNGD
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANEUPLOIDY
ANIMALS
ANTINEOPLASTIC DRUGS
AROMATICS
BENZOPYRENE
BIOLOGICAL EFFECTS
CELL DIVISION
CELL TRANSFORMATIONS
CONDENSED AROMATICS
CORRELATIONS
DNA REPLICATION
DRUGS
HAMSTERS
HYDROCARBONS
MAMMALS
MITOSIS
NUCLEIC ACID REPLICATION
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
PLOIDY
RODENTS
SIDE EFFECTS
VERTEBRATES