Studies of an S9-based metabolic activation system used in the mouse lymphoma L5178Y cell mutation assay

The genotoxic potential of Aquateric® Aqueous Enteric Coating was evaluated in the Ames test, the mouse lymphoma mutation assay, and the mouse micronucleus test. Aquateric was not mu-tagenic when tested in Salmonella typhimurium cell strains TA98, TA100, TA1535, TA1537, TA1538, with or without metabolic activation. A mouse lymphoma assay was conducted at concentrations ranging from 116 to 2000 μg/ml and 116 to 1250 μg/ml in the absence and presence of metabolic activation, respectively. No increased mutant frequencies were noted for any concentration tested. Aquateric was tested in the mouse micronucleus assay at a single oral dose of 7200 mg/kg Aquateric (equivalent to 5000 mg/kg cellulose acetate phthalate, the major ingredient) and bone marrow was harvested at 24, 48, and 72 hours after treatment. There was no significant increase in the number of mouse bone marrow mi-cronucleated polychromatic erythrocytes in Aquateric-treated animals at any of the harvest times. Based on the negative results in the Ames test, the mouse lymphoma mutation assay, and the mouse micronucleus test, it was concluded that Aquateric is not genotoxic.

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A statistical method for analysis of mouse lymphoma L5178Y cell TK locus forward mutation assay

Mutation Research/Environmental Mutagenesis and Related Subjects ◽

10.1016/0165-1161(82)90004-8 ◽

1982 ◽

Vol 97 (5) ◽

pp. 371-392 ◽

Cited By ~ 13

Author(s):

Joseph D. Irr ◽

Ronald D. Snee

Keyword(s):

Statistical Method ◽

L5178y Cell ◽

Mutation Assay ◽

Forward Mutation ◽

Mouse Lymphoma

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Recommendations for spacing of test chemical concentrations in the mouse lymphoma tk mutation assay (MLA)

Mutation Research/Genetic Toxicology and Environmental Mutagenesis ◽

10.1016/s1383-5718(98)00056-4 ◽

1998 ◽

Vol 415 (1-2) ◽

pp. 159-163 ◽

Cited By ~ 8

Author(s):

David J. Kirkland ◽

Julie Clements

Keyword(s):

Test Chemical ◽

Mutation Assay ◽

Mouse Lymphoma

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521 HUMAN HEMOGLOBIN IN VIVO SOMATIC CELL MUTATION ASSAY

Pediatric Research ◽

10.1203/00006450-197804001-00526 ◽

1978 ◽

Vol 12 ◽

pp. 450-450

Author(s):

Richard Doherty ◽

Elsa Cernichiari

Keyword(s):

Somatic Cell ◽

Human Hemoglobin ◽

Cell Mutation ◽

Mutation Assay

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In vitro genotoxicity evaluation and metabolic study of residual glutaraldehyde in animal-derived biomaterials

Regenerative Biomaterials ◽

10.1093/rb/rbaa041 ◽

2020 ◽

Vol 7 (6) ◽

pp. 619-625

Author(s):

Jianfeng Shi ◽

Huan Lian ◽

Yuanli Huang ◽

Danmei Zhao ◽

Han Wang ◽

...

Keyword(s):

Metabolic Activation ◽

Chemical Toxicity ◽

Major Health ◽

Mouse Lymphoma Assay ◽

Metabolic Mechanism ◽

Mutagenic Effects ◽

Mouse Lymphoma ◽

General Balance ◽

In Vitro Genotoxicity

Abstract Glutaraldehyde (GA) is an important additive that is mainly used in animal-derived biomaterials to improve their mechanical and antimicrobial capacities. However, GA chemical toxicity and the metabolic mechanism remain relatively unknown. Therefore, residual GA has always been a major health risk consideration for animal-derived medical devices. In this study, extracts of three bio-patches were tested via the GA determination test and mouse lymphoma assay (MLA). The results showed that dissolved GA was a potential mutagen, which could induce significant cytotoxic and mutagenic effects in mouse lymphoma cells. These toxic reactions were relieved by the S9 metabolic activation (MA) system. Furthermore, we confirmed that GA concentration decreased and glutaric acid was generated during the catalytic process. We revealed GA could be oxidized via cytochrome P450 which was the main metabolic factor of S9. We found that even though GA was possibly responsible for positive reactions of animal-derived biomaterials’ biocompatibility evaluation, it may not represent the real situation occurring in human bodies, owing to the presence of various detoxification mechanisms including the S9 system. Overall, in order to achieve a general balance between risk management and practical application, rational decisions based on comprehensive analyses must be considered.

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