Related Experiment Video
Updated: Aug 14, 2026
Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
Inhibition of the activity of mouse natural killer cells by urethan
Abstract:
The effect of the carcinogen urethan on the natural killer (NK) activity of spleen cells from inbred A/J mice was studied. Urethan (1 mg/g) inoculated into 6- to 8-week-old A/J mice produced considerable depression of cytotoxic activity of spleen cells against YAC-1 or RL male 1 tumor cells. This effect was biphasic. Initial depression of NK activity was observed 1 day after urethan treatment, reactivity normalized at 4 days, and then a second, more profound depression was seen around 7-8 days, which persisted for 14-18 days. In contrast, lymphoproliferative responses of spleen cells to mitogens were only transiently depressed after urethan treatment and were in the normal range during the second period of marked depression of NK activity. Urethan appeared to have an even more profound effect on NK activity when given to very young mice (5-17 days old). After one or two injections of urethan, very low splenic NK activity was found 6 and 7 weeks later. The carcinogenic effects of urethan were also more striking in these young recipients, with multiple tumors observed in the lungs at the time of cytotoxicity testing. Inoculation of adult urethan-treated mice with the interferon inducer polyinosinic-polycytidylic acid, boosted NK activity to the same extent as seen with normal mice, which suggested that pre-NK cells are resistant to the effects of urethan. The present data agree with the hypothesis that the ability of a chemical to depress NK cell activity is an important factor in its carcinogenic activity.
Insights
The carcinogen urethan significantly depresses natural killer (NK) cell activity in mice, particularly in young animals. This NK cell suppression is linked to urethan's carcinogenic effects, suggesting a role in tumor development.
Area of Science:
- Immunology
- Toxicology
- Carcinogenesis
Background:
- Natural killer (NK) cells are crucial for innate immunity against tumors.
- Urethan is a known carcinogen with poorly understood mechanisms of action.
- The impact of urethan on immune cell function, specifically NK activity, requires further investigation.
Purpose of the Study:
- To investigate the effect of the carcinogen urethan on NK cell activity in A/J mice.
- To determine if urethan-induced NK cell depression correlates with its carcinogenic potential.
- To explore the susceptibility of different age groups and NK cell precursors to urethan.
Main Methods:
- Spleen cells from urethan-treated A/J mice were assessed for cytotoxic activity against tumor cell lines.
- Lymphoproliferative responses to mitogens were measured.
- NK activity was evaluated in young mice and adult mice treated with an interferon inducer.
Main Results:
- Urethan caused a biphasic depression of NK activity, with a profound and prolonged decrease observed 7-18 days post-treatment.
- Lymphoproliferative responses were only transiently affected.
- Young mice exhibited severe and lasting NK cell suppression, along with increased tumor incidence.
- Pre-NK cells appeared resistant to urethan's suppressive effects.
Conclusions:
- Urethan significantly impairs NK cell activity in a time- and age-dependent manner.
- The depression of NK cell activity by urethan is strongly associated with its carcinogenic effects.
- NK cell activity modulation may be a key factor in urethan-induced carcinogenesis.
