Recommended protocols based on a survey of current practice in genotoxicity testing laboratories: II. Mutation in Chinese hamster ovary, V79 Chinese hamster lung and L5178Y mouse lymphoma cells

Nestmann, Earle R.; Brillinger, R.L.; Gilman, J. P. W.; Rudd, Colette J.; Swierenga, S.H.H.

doi:10.1016/0027-5107(91)90048-s

Cited by 41 publications

(13 citation statements)

References 25 publications

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“…The Thymidine Kinase (TK) assay was used to determine the mutagenic and clastogenic potential of HbMP‐700 supernatant using the mouse lymphoma cell line L5178Y. The assay detects mutations at the TK locus (TK +/ − to TK − / − ) due to different genetic alterations such as base pair changes, frame shift mutations, and small and large nonlethal deletions of the relevant chromosome . TK expressing cells will incorporate the pyrimidine analogue trifluoro‐thymidine (TFT) leading to cell death due to an inhibition of cellular metabolism.…”

Section: Resultsmentioning

confidence: 99%

Preclinical In Vitro Safety Investigations of Submicron Sized Hemoglobin Based Oxygen Carrier HbMP‐700

et al. 2018

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Hemoglobin-based oxygen carriers (HBOCs) are being developed as oxygen and plasma volume-expanding therapeutics though their potential to promote oxidative tissue injury and nitric oxide (NO) scavenging combined with vasoconstriction has raised safety concerns. Therefore, we focused on these aspects during preclinical studies performed with the recently introduced hemoglobin microparticles (HbMP-700). Besides oxidative stress, we investigated possible vasoconstrictory influence of HBOCs as well as genetic toxicity. The novel developed HbMP-700 presented here provides a high oxygen affinity which prevents premature oxygen oversupply and avoids vasoconstriction of small blood vessels in vitro. The size of these particles is 700 nm (larger than 100 nm and smaller than 1000 nm) in order to prevent penetration through the blood vessel's endothelial gaps, NO-scavenging, and to avoid phagocytosis of large particles. We expect that the HbMP-700 meets the sophisticated requirements as a universal blood substitute.

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Section: Resultsmentioning

confidence: 99%

Preclinical In Vitro Safety Investigations of Submicron Sized Hemoglobin Based Oxygen Carrier HbMP‐700

et al. 2018

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“…NTA was dissolved in a NaOH 1 N sterile solution at the initial concentration of 100 mg/ml, then diluted in RPMI medium either at 10 mg/ml (first assay) or 6.5 mg/ml (second assay), giving the final concentration of 1,000 or 650 lg/ml, respectively, when added at 10% in culture medium. The highest retained concentration did not present any increase in the osmolality superior to 50 mOsm/kg in respect to the solvent control [Scott et al, 1991] or a pH inferior to 6 [Nestmann et al, 1991].…”

Section: Mutation Assay At the Tk Locus In L5178y Mouse Lymphoma Cellmentioning

confidence: 94%

Characterization of the genotoxicity of nitrilotriacetic acid

Nesslany

Simar-Meintières

Watzinger

et al. 2008

Environ and Mol Mutagen

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The chelating agent nitrilotriacetic acid (NTA), classified as an epigenetic rodent carcinogen, was assessed in the in vivo rodent Comet assay on isolated kidney cells. Unexpected potent increases in DNA damage were obtained in both the short (3-6 hr) and long-term (22-26 hr) expression times after a single oral treatment at 1,000-2,000 mg/kg bw. NTA was assayed in the Ames test using TA1537, TA98, TA100, and TA102 tester strains, and in the in vitro micronucleus assay on L5178Y mouse lymphoma cells and on CTLL2 and CTLL2/Bcl2 cells coupled to the apoptosis measurement, both with and without metabolic activation by aroclor 1254-induced liver or kidney rat S9-mix. Whatever the S9 origin, neither genotoxicity nor apoptosis was detected, while a strong increase in the micronuclei formation was observed without S9 without any apoptosis induction. The direct genotoxicity of NTA was confirmed in the mouse lymphoma tk+/- gene mutation assay and in the chromosomal aberrations test on human lymphocytes. When tested in combination with an excess of Ca2+, NTA gave negative results on L5178Y mouse lymphoma cells in the in vitro Comet and micronucleus assays but still induced DNA damage on rat primary kidney cells. The higher sensitivity of renal cells to Ca2+ variations could explained the positive response observed in vivo. The carcinogenicity of NTA could be a consequence of the survival of kidney cells to intracellular variations of Ca2+, leading to a local and indirect genotoxicity. This suggests that threshold dose exists beyond which tumor-generating events will be displayed.

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“…The HPRT assay was performed with V79 cells (lung fibroblasts from male Chinese hamster) according to established methods [19,16]. The cells were incubated for 4 h in serum-free culture medium (RPMI 1640 medium with 100 U/mL penicillin and 100 lg/mL streptomycin) and the stated enniatin B concentrations, either in the presence or in the absence of an external metabolizing enzyme system (S9 mix from rat liver).…”

Section: Hprt Assaymentioning

confidence: 99%

The Fusarium toxin enniatin B exerts no genotoxic activity, but pronounced cytotoxicity in vitro

Behm

Degen

Föllmann

2009

Molecular Nutrition Food Res

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Enniatin B, a fungal metabolite produced by various Fusarium strains, is a frequent contaminant in cereals used for human foods and animal feeds, but, so far very limited data are available on its toxicity. The aim of this study was to investigate the effects of enniatin B in a battery of short-term tests to evaluate its genotoxic potential. In Salmonella typhimurium assays (Ames assay) with the strains TA 98, TA 100, TA 102, and TA 104, both in the presence and absence of an external metabolizing enzyme system (rat liver S9), no mutagenicity was detected up to toxic levels (100 microM) of enniatin B. Likewise, mutagenicity tests in mammalian cells, i. e., the hypoxanthin-guanin-phosphoribosyl-transferase (HPRT) assay with V79 cells performed with and without S9 mix, did not reveal a significant increase in mutant frequency for enniatin B up to 30 microM, a cytotoxic concentration. Additional tests on other types of genotoxicity, i. e., clastogenicity and chromosomal damage, were conducted in V79 cells, applying the alkaline single cell gel electrophoresis (Comet assay with and without FPG, formamidopyrimidine DNA glycosylase, enzyme) and the micronucleus assay. None of these assays revealed a significant genotoxic potential of enniatin B. However, enniatin B exerts pronounced cytotoxic effects in V79 cells as determined by neutral red uptake assay for 48 h exposure: The IC(20) and IC(50) values of 1.5 and 4 microM, are higher than those of the more potent Fusarium toxin deoxynivalenol (IC(20) 0.6 microM, IC(50) of 0.8 microM), but in a similar range as values reported for cytotoxicity of enniatin B in various tumor cell lines. In summary, despite an apparent lack of genotoxic activity, enniatin B can exert biological activity at low micromolar concentrations in mammalian cells.

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Recommended protocols based on a survey of current practice in genotoxicity testing laboratories: II. Mutation in Chinese hamster ovary, V79 Chinese hamster lung and L5178Y mouse lymphoma cells

Cited by 41 publications

References 25 publications

Preclinical In Vitro Safety Investigations of Submicron Sized Hemoglobin Based Oxygen Carrier HbMP‐700

Preclinical In Vitro Safety Investigations of Submicron Sized Hemoglobin Based Oxygen Carrier HbMP‐700

Characterization of the genotoxicity of nitrilotriacetic acid

The Fusarium toxin enniatin B exerts no genotoxic activity, but pronounced cytotoxicity in vitro

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