The molecular mechanisms of immune suppression by two impurities in the organosphosphate pesticides, malathion, acephate and fenitrothion, O,O,S-trimethyl phosphorothioate (OOS-TMP) and O,S,S-trimethyl phosphorodithioate, will be examined. Macrophaages, through cell separation and reconstitution experiments, have been shown to be the lymphoid cell most affected by OOS-TMP treatment. The blockage in the maturation of macrophages which occurs following acute administration of OOS-TMP will be identified. Studies will include changes in macrophage cell surface markers, Ia, Mac-1, Mac-2 and F4/80, functional activity and secretory products. The inhibitory effect of a structural analog OSS-TMP on cytolytic effector function will be examined in detail using functionally defined cytotoxic T lymphocytes (CTL) and other cytolytic effector cells. The site(s) of the blockade of murine CTL function will be determined using conjugate formation and Ca2+ pulse techniques. The molecular sites will be identified using radiolabelled OSS-TMP and biochemical analyses. In addition, an adaptation of a colorimetric assay (dye reduction) for cell viability will be investigated for its suitability as a screening assay for the cytotoxic and cytostatic activities of environmental toxicants. This assay may be an alternative to the standard trypan blue exclusion method for assessing cell viability.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29ES004337-06
Application #
3465159
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
1986-09-01
Project End
1992-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Los Angeles County Health Services Department
Department
Type
DUNS #
613990808
City
Los Angeles
State
CA
Country
United States
Zip Code
90012