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Different chemosensitivities of rat 3Y1 fibroblasts transformed by various agents in vitro
Y Kido1, T Mitsudomi, H Kuwano
1Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abstract:
Alterations of chemosensitivities associated with transformation of rat 3Y1 fibroblasts were compared among various agents, including either adenovirus type 12 (Ad12-3Y1), the E1A region of adenovirus type 12 (E1A-3Y1), mouse polyoma virus (Py-3Y1), Simian virus 40 (SV-3Y1), Rous avian sarcoma virus (SR-3Y1), plasmid DNA carrying v-Ha-ras oncogene (HR-3Y1), or N-methyl-N'-nitro-N-nitrosoguanidine (NG-3Y1), with untransformed 3Y1 fibroblasts, using a semiautomated non-clonogenic MTT assay. IC50 values were compared for each drug in each cell line. Among the different cell lines, untransformed 3Y1 cells were the most resistant to cisplatin (CDDP), adriamycin (ADM), carboquone (CQ), bleomycin (BLM), mitomycin C (MMC) and 4-hydroperoxy cyclophosphamide (4-hp-CPA). On the other hand, E1A-3Y1 cells were more resistant to vincristine (VCR) and NG-3Y1 and Ad12-3Y1 were more resistant to 5-fluorouracil (5-FU) than untransformed 3Y1 cells. These transformed lines did not display any cross-resistance to other drugs. The dissociation of chemosensitivities between Ad12-3Y1 and E1A-3Y1 to ADM, VCR and 5-FU was recognized. These results suggested that some of these transforming agents may alter the chemosensitivities of anticancer drugs.
Insights
Viral and oncogene transformation of rat fibroblasts altered anticancer drug sensitivities. Some transformed cells showed increased resistance to specific agents like 5-fluorouracil, while others did not exhibit cross-resistance, suggesting targeted chemosensitivity modulation.
Area of Science:
- Oncology
- Virology
- Cell Biology
Background:
- Cell transformation by viral agents or oncogenes can alter cellular characteristics.
- Understanding changes in chemosensitivity is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate how viral transformation and oncogene expression affect the chemosensitivity of rat 3Y1 fibroblasts.
- To compare the chemosensitivity profiles of various transformed cell lines against a panel of anticancer drugs.
Main Methods:
- Utilized a semiautomated non-clonogenic MTT assay to determine IC50 values.
- Compared chemosensitivities of untransformed 3Y1 fibroblasts with cell lines transformed by adenovirus type 12, E1A region of adenovirus type 12, mouse polyoma virus, Simian virus 40, Rous avian sarcoma virus, v-Ha-ras oncogene, and N-methyl-N'-nitro-N-nitrosoguanidine.
Main Results:
- Untransformed 3Y1 cells exhibited the highest resistance to cisplatin, adriamycin, carboquone, bleomycin, mitomycin C, and 4-hydroperoxy cyclophosphamide.
- E1A-3Y1 cells showed increased resistance to vincristine, while NG-3Y1 and Ad12-3Y1 cells were more resistant to 5-fluorouracil.
- Transformed cell lines did not display cross-resistance to other tested drugs, and distinct chemosensitivity patterns were observed between Ad12-3Y1 and E1A-3Y1 cells.
Conclusions:
- Specific transforming agents can modulate the chemosensitivity of fibroblasts to anticancer drugs.
- The E1A region of adenovirus type 12 and other viral/oncogenic transformations induce distinct alterations in drug resistance profiles.