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Published on: May 12, 2020
The Toxicity of Dimethyl Sulfoxide Combined with the Alkylating Agent MNU on Mice: Focusing on Mortality and Activity
Weiming Yan1, Qiurui He2, Lin Xiao1
1Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350025, People's Republic of China.
Objective:
Dimethyl sulfoxide (DMSO) is known to enhance the absorption of chemicals. This study investigated the effects of DMSO in combination with the alkylating agent, N-methyl-N-nitrosourea (MNU), on the activity and mortality of mice, providing foundational data for solvent mixture use and health impact assessment.
Methods:
Twelve male SPF C57BL/6J mice were divided into three groups (n=4): DMSO group (D), DMSO combined with low-dose (L), and high-dose MNU group (H). Mice in D received intraperitoneal injections of pure DMSO solution at 12 mL/kg. The L or D group was injected with a DMSO solution containing 40 mg/kg or 60 mg/kg MNU at 12 mL/kg, respectively. Mice were monitored for changes in body weight, activity levels (walking, body stretching, fur condition), and mortality at various time points.
Results:
Pre-injection, all groups showed no statistical differences in weight or DMSO dose, while the MNU injection dose was significantly different (H>L>D). Within 2 hours post-injection, all mice except one in the D group exhibited reduced mobility, hunched posture, and lethargy. Mortality progressed rapidly, with one D and two L mice dying by 12 hours, followed by additional deaths (one D, two L, and two H mice) at 24 hours. By 36 hours, all mice in L and H groups had died, while one D mouse recovered normal activity. At the 48-hour endpoint, only one D mouse survived with normal behavior. No significant differences in weight, activity levels and mortality changes were observed in surviving mice throughout the study period.
Conclusion:
DMSO has certain toxicity, and when combined with alkylating agents such as MNU, it can lead to reduced activity and an increased mortality rate in mice. It is recommended to closely monitor the mice during the use of such reagents and to establish appropriate research observation protocols.
Insights
Dimethyl sulfoxide (DMSO) combined with N-methyl-N-nitrosourea (MNU) significantly increased mouse mortality and reduced activity. Careful monitoring and research protocols are essential when using these agents together.
Area of Science:
- Toxicology
- Pharmacology
- Animal Models
Background:
- Dimethyl sulfoxide (DMSO) is a widely used solvent known for its ability to enhance chemical absorption.
- Alkylating agents, such as N-methyl-N-nitrosourea (MNU), are used in research but can have significant toxic effects.
- Understanding the combined effects of solvents and active agents is crucial for safe research practices and health impact assessments.
Purpose of the Study:
- To investigate the combined effects of DMSO and MNU on mouse activity and mortality.
- To provide foundational data for the safe use of solvent mixtures in research.
- To inform health impact assessments related to combined chemical exposures.
Main Methods:
- Male C57BL/6J mice were divided into three groups: DMSO only, DMSO with low-dose MNU, and DMSO with high-dose MNU.
- Mice received intraperitoneal injections of DMSO or DMSO-MNU mixtures at specified doses.
- Parameters monitored included body weight, activity levels (mobility, posture, fur condition), and mortality over 48 hours.
Main Results:
- Within 2 hours post-injection, most mice exhibited reduced mobility and lethargy.
- Mortality increased rapidly, with all mice in the MNU groups dying by 36 hours.
- One mouse in the DMSO-only group survived and recovered normal activity by 48 hours, while others in this group also showed signs of toxicity.
Conclusions:
- DMSO exhibits inherent toxicity and exacerbates the toxicity of MNU, leading to significant reductions in activity and increased mortality in mice.
- Close monitoring of animals and the establishment of appropriate research protocols are recommended when using DMSO in combination with alkylating agents like MNU.

