The Toxicity of Dimethyl Sulfoxide Combined with the Alkylating Agent MNU on Mice: Focusing on Mortality and Activity Impairment.

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.