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Differential inducibility of chromosome aberrations and sister-chromatid exchanges by indirect mutagens in various
Abstract:
A total of 17 cultured mammalian cell lines of various types was investigated for the inducibility of chromosome aberrations (CAs) and sister-chromatid exchanges (SCEs) after exposure to 3 direct mutagens, cyclophosphamide (CP), dimethylnitrosamine (DMN) and benzo[a]pyrene (BP), without extrinsic metabolizing factors. The following cell lines were highly sensitive to CP as estimated by the dose-dependent increase of either CAs or SCEs, or both: 4 rat ascites hepatomas (AH66-B, AH66-C, AH70B, AH109A), 3 rat esophageal tumors (R1, R2, R3), the Yoshida sarcoma (YS), a Chinese hamster embryonic cell line (B-13), and a human embryonic (HE2236) cell line. 1 golden-hamster embryonic (GHE), 1 human embryonic (HE2144) and 1 human esophageal tumor (TH) cell line were moderately sensitive to CP in terms of the yield of SCEs, though they showed rather low sensitivity when measured by the frequency of CAs. 2 Chinese hamster (CHO-K1, CHL) and 1 human lymphoma (P3HR-1) cell lines were much less sensitive or almost insensitive with respect to the yield of both CAs and SCEs. Considering the above results and taking some other experimental conditions into account, 7 cell lines, including another Chinese hamster cell line (Don 6), were similarly investigated with DMN and BP. The results indicated that AH66-B, which was highly sensitive to CP, was also sensitive to DMN and BP, and that the CP-sensitive R1 and R3 were responsive to DMN. While YS, B-13, Don 6 and P3HR-1 did not show any significant response to DMN, a considerable increment of SCEs was noted in B-13 after treatment with BP, GHE was also notable for its high sensitivity to BP, showing an apparently dose-dependent increase of both CAs and SCEs. HE2144 exhibited a slightly increased rate of SCEs after exposure to BP.
Insights
This study investigated 17 mammalian cell lines for their sensitivity to chromosome aberrations (CAs) and sister-chromatid exchanges (SCEs) induced by cyclophosphamide (CP), dimethylnitrosamine (DMN), and benzo[a]pyrene (BP). Certain rat and human cell lines showed high sensitivity to CP, while others responded differently to DMN and BP.
Area of Science:
- Toxicology and Mutagenesis
- Cell Biology and Genetics
Background:
- Mammalian cell lines are crucial models for assessing the genotoxic potential of chemical compounds.
- Understanding differential cellular responses to mutagens is vital for predicting human health risks.
Purpose of the Study:
- To evaluate the inducibility of chromosome aberrations (CAs) and sister-chromatid exchanges (SCEs) in various cultured mammalian cell lines.
- To determine the sensitivity of these cell lines to three direct mutagens: cyclophosphamide (CP), dimethylnitrosamine (DMN), and benzo[a]pyrene (BP).
Main Methods:
- Investigated 17 diverse mammalian cell lines for genotoxicity.
- Exposed cells to cyclophosphamide (CP), dimethylnitrosamine (DMN), and benzo[a]pyrene (BP) without external metabolic activation.
- Quantified chromosome aberrations (CAs) and sister-chromatid exchanges (SCEs) as indicators of mutagenic response.
Main Results:
- Several rat hepatoma and esophageal tumor cell lines, along with Yoshida sarcoma and Chinese hamster/human embryonic cell lines, exhibited high sensitivity to CP-induced CAs and/or SCEs.
- AH66-B cells were sensitive to CP, DMN, and BP. CP-sensitive rat esophageal tumor lines (R1, R3) responded to DMN.
- Chinese hamster embryonic (B-13) and golden hamster embryonic (GHE) cell lines showed notable sensitivity to benzo[a]pyrene (BP)-induced SCEs and CAs/SCEs, respectively.
Conclusions:
- Mammalian cell lines display varied sensitivities to direct-acting mutagens, highlighting the importance of cell line selection in genotoxicity testing.
- Specific cell lines, such as AH66-B and GHE, demonstrate broad responsiveness to different mutagens, making them valuable tools for toxicological screening.
- The study provides a basis for selecting sensitive cell lines for future mutagenicity assessments of environmental and industrial chemicals.