Human and rodent transformed cells are more sensitive to in vitro induction of SCE by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) than normal cells

Abstract

The sensitivity to sister chromatid exchange (SCE) induction by N-methyl-nitro-N'-nitrosoguanidine (MNNG) in human, mouse, Chinese hamster, and Syrian hamster normal cell strains and in permanent transformed cell lines of the same species was compared. Exponentially growing or growth-inhibited cultures of permanent cell lines transformed spontaneously or by chemical carcinogen or oncogenic virus responded with a higher SCE frequency after MNNG treatment than did normal diploid cell strains. Compared with the normals, exponentially growing Simian virus 40 transformed human fibroblast GM637 had the highest SCE frequency, followed by mouse cell line alpha L929 and Chinese hamster V79-4; the least sensitive were two Syrian hamster cell lines, OBP, derived from transformation of embryo cells with benzo(a)pyrene, and BHK, a spontaneously transformed baby hamster kidney line. Similar results were obtained with cultures arrested in G1 with glutamine-arginine deficient medium. The SCE response observed with transformed cells to carcinogen probably reflects cellular changes associated with the transformed state, such as shortening of the cell cycle, excision repair deficiency, or an increase in DNA replicon size. The current results demonstrating a difference in SCE induction between normal and malignant cells are important since normal or transformed cultured cells are utilized to assess potentially deleterious environmental agents, particularly carcinogens. In general, SCE induction by a specific direct acting carcinogen may be a useful approach for identifying transformed cells with the ability to produce tumors.

Chromodomain helicase DNA‐binding protein 2 affects the repair of X‐ray and UV‐Induced DNA damage

“…However, in clonogenic assays, the colonyforming capacity of the Chd2 mutant MEFs was significantly compromised after treatment with both the DNA damaging agents. Previous studies have shown that the expression of SV40 large T-antigen in cells renders them more susceptible to DNA damage [Popescu et al, 1983;Digweed et al, 2002]. The differences in the survival capacity of primary fibroblasts and SV40 transformed fibroblasts also underline the complexity of genetic pathways that function in DNA damage responses in mammalian cells.…”

Long‐term survival estimates for imatinib versus interferon‐α plus low‐dose cytarabine for patients with newly diagnosed chronic‐phase chronic myeloid leukemia

“…However, in clonogenic assays, the colony‐forming capacity of the Chd2 mutant MEFs was significantly compromised after treatment with both the DNA damaging agents. Previous studies have shown that the expression of SV40 large T‐antigen in cells renders them more susceptible to DNA damage [Popescu et al,1983; Digweed et al,2002]. The differences in the survival capacity of primary fibroblasts and SV40 transformed fibroblasts also underline the complexity of genetic pathways that function in DNA damage responses in mammalian cells.…”