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Comparative effectiveness of lymphotoxin anticarcinogenic and tumor cell growth-inhibitory activities
Abstract:
Prevention of ultraviolet radiation- or chemical carcinogen-induced morphologic transformation and inhibition of tumor-producing transformed cell growth by lymphotoxin and by normal spleen leukocytes were quantitatively compared to define the antineoplastic activity spectra of these natural immune mediators. When Syrian golden hamster embryo cells seeded for colony formation in culture dishes were treated simultaneously with carcinogen and lymphotoxin, the number of morphologically transformed cell colonies was irreversibly reduced by 50% in the presence of 6 units of lymphotoxin/ml. Lymphotoxin inhibition of tumor cell growth, however, was reversible and 50% reduction in tumor cell growth in three transformed lines required 124, 330, and 477 units/ml. Thus, the anticarcinogenic activity of lymphotoxin can be 20-fold or more greater than its tumor growth-inhibitory activity. Similarly spleen leukocytes also were more effective as an anticarcinogen than as an inhibitor of tumor cell growth, consistent with previous observations that naturally occurring spleen leukocyte antineoplastic activity may result from lymphotoxin secretion.
Insights
Lymphotoxin and spleen leukocytes show potent anticarcinogenic activity, effectively preventing cell transformation. Their ability to inhibit tumor growth is significantly less potent than their cancer prevention capabilities.
Area of Science:
- Immunology
- Cancer Biology
- Cell Biology
Background:
- Natural immune mediators like lymphotoxin and spleen leukocytes possess antineoplastic properties.
- Understanding the specific activity spectra of these mediators is crucial for developing novel cancer therapies.
Purpose of the Study:
- To quantitatively compare the anticarcinogenic and tumor growth-inhibitory activities of lymphotoxin and normal spleen leukocytes.
- To define the antineoplastic activity spectra of these natural immune mediators.
Main Methods:
- Syrian golden hamster embryo cells were cultured and treated with carcinogens and varying concentrations of lymphotoxin.
- Morphologic transformation and tumor cell growth were quantitatively assessed in the presence of lymphotoxin and spleen leukocytes.
Main Results:
- Lymphotoxin significantly inhibited carcinogen-induced morphologic transformation by 50% at 6 units/ml.
- Lymphotoxin's inhibition of tumor cell growth was reversible and required much higher concentrations (124-477 units/ml) for 50% reduction.
- Spleen leukocytes demonstrated greater efficacy as anticarcinogens compared to their tumor growth-inhibitory effects.
Conclusions:
- Lymphotoxin exhibits a significantly greater anticarcinogenic activity (over 20-fold) than its tumor growth-inhibitory activity.
- Spleen leukocyte antineoplastic activity may stem from lymphotoxin secretion, highlighting its role in natural cancer prevention.