Immunotoxicological characteristics of sodium methyldithiocarbamate.
This study was conducted to assess immunotoxicological effects and selected general toxicological effects of sodium methyldithiocarbamate (SMD). Initially, the compound was administered orally to female B6C3F1 mice at 300 mg/kg/day for 3, 5, 10, or 14 days. Body, liver, kidney, spleen, and thymus weights were measured. Selected hematological and bone marrow parameters were examined. Flow cytometric analysis was used to assess changes in lymphocyte subpopulations in the thymus and spleen, and production of antibody-forming cells in vitro was measured. Major effects included decreased thymus weight at all time points; increased spleen weight after 10 or 14 days of exposure, increased bone marrow cellularity after 10 or 14 days of exposure, significant decreases in mature lymphocyte subpopulations which were greater in the thymus than in the spleen, relatively selective depletion of the major subpopulation of thymocytes (CD4+CD8+), and decreased body weight. Overall patterns of changes were consistent with the conclusion that SMD rapidly depletes most CD4+CD8+ thymocytes, more slowly depletes a smaller number of mature lymphocytes in the thymus and spleen, and induces compensatory and/or detoxication mechanisms after 10-14 days of exposure. Subsequent experiments were done to assess selected immune function parameters. SMD at 50-300 mg/kg/day for 7 days caused substantial, dose-dependent suppression of NK cell activity. No suppression of antibody production in vivo or splenocyte responses to mitogens or allogeneic lymphocytes in vitro was detected. NK cell activity, thymus weight, and CD4+CD8+ thymocyte numbers were suppressed by dermal administration of SMD.(ABSTRACT TRUNCATED AT 250 WORDS)
Pruett
S B
SB
Department of Biological Sciences, Mississippi State University, Mississippi State 39762.
Barnes
D B
DB
Han
Y C
YC
Munson
A E
AE
D000287:Administration, Topical; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000969:Antinematodal Agents / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D005260:Female; D007075:Immunoglobulin M / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D016131:Lymphocyte Subsets; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D012869:Skin Absorption; D013859:Thiocarbamates / Q000008:administration & dosage / Q000633:toxicity*
D000969:Antinematodal Agents; D007075:Immunoglobulin M; D013859:Thiocarbamates; C008435:methyldithiocarbamate