Immune alterations in rats following subacute exposure to tributyltin oxide.
Adult male Fischer 344 rats were dosed by oral gavage with bis(tri-n-butyltin)oxide (TBTO) in peanut oil for 10 consecutive days, at dosages ranging from 1.25 to 15 mg/kg/day. Other groups of rats were dosed daily for 10 days by oral gavage with cyclophosphamide (CY) at dosages ranging from 0.75 to 6 mg/kg/day. These rats served as positive controls for the immune assays employed. The immune function parameters examined included the following: delayed-type hypersensitivity (DTH) and antibody responses to bovine serum albumin (BSA), primary antibody responses to sheep red blood cells (SRBC) and trinitrophenyl lipopolysaccharide (TNP-LPS) and enumeration of splenic lymphocyte populations. The DTH and antibody responses to BSA were not affected by TBTO exposure; however these responses were suppressed in rats dosed with CY at 6 mg/kg/day. The plaque forming cell (PFC) response to the T cell-dependent antigen SRBC was enhanced in rats dosed with TBTO at from 5 to 15 mg/kg/day. On the other hand, the PFC response to the T cell-independent antigen TNP-LPS was unaffected by TBTO exposure. Rats dosed with CY had suppressed PFC responses to SRBC and TNP-LPS at dosages of 3 and 6 mg/kg/day, respectively. Enumeration of splenic lymphocyte populations from TBTO-exposed rats revealed a reduction in OX8- but not W3/25- or IgG-positive cells. These results, as well as results from an earlier study from this lab, suggest that T lymphocytes are a primary target for TBTO-induced immune alterations and that the enhancement of the PFC response to SRBC in TBTO-exposed rats may be mediated by alterations in the suppressor (OX8-positive) T lymphocyte population.
Smialowicz
R J
RJ
Pulmonary Toxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Riddle
M M
MM
Rogers
R R
RR
Leubke
R W
RW
Copeland
C B
CB
Ernst
G G
GG
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000955:Antigens, T-Independent / Q000276:immunology; D003520:Cyclophosphamide / Q000276:immunology / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006462:Hemolytic Plaque Technique; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D014220:Trialkyltin Compounds / Q000276:immunology* / Q000494:pharmacology
D000955:Antigens, T-Independent; D007166:Immunosuppressive Agents; D014220:Trialkyltin Compounds; C005961:bis(tri-n-butyltin)oxide; D003520:Cyclophosphamide