Lymphocyte-assay

Preston, R.J., San Sebastian, J.R. and McFee, A.F. (1987). The in vitro human lymphocyte assay for assessing the clastogenicity of chemical agents. Mutation Res. 189 175-183. 

Fertility and early embryonic development rhesus monkeys Developmental rhesus monkeys Prenatal and postnatal development none Genetic toxicology Ames test, in vitro transformation assay, human peripheral blood lymphocyte assay Carcinogenicity none... 

Epstein M, Wright JM. Severe multisystem disease caused by trimethoprim-sulfamethoxazole possible role of an in vitro lymphocyte assay. The Journal of allergy and clinical Immunology. 1990 Sep,-86(3 Pt 1) 416-7. 

Southern Caribbean collections of L. majuscula are a common source of a highly antiproliferative and immunosuppressive lipopeptide known as microcolin A (96). Activity in a mixed lymphocyte assay was originally used to direct the isolation of this metabolite and structure elucidation followed from normal procedures. Toxicity apparently prevented its development as a therapeutic. Stereochemistry at the two aliphatic methyl groups was problematic and finally succumbed to comparisons with synthetic materials of defined configurations. " Microcolin illustrates a broad class of marine cyanobacterial metabolite, which includes several closely related microcolins, majusculamide D, and deoxymajuscualmide... 

B. Radiation Injury Probable. Anorexia, nausea, and vomiting are the primary prodromal symptoms associated with radiation injury. Priority for further evaluation will be assigned after all life-threatening injuries have been stabilized. Casualties in this category will not require any medical treatment within the first few days for their radiation injuries. Evidence to support the diagnosis of significant radiation injury in the absence of bums and trauma may be obtained from lymphocyte assays taken over the next 2 days. If the evidence indicates that a significant radiation injury was received, these casualties need to be monitored for pancytopenic complications. 

Mice were immunized by s.c. injection of 0.2 ml of test formulation (25 p,g of the antigen OVA and varying doses of the test adjuvants) on days 0 and 14. Mice were bled and sera collected for antibody titer determination one week after the second immunization. Several other schedules of immunization have been reported in the literature. Splenic mononuclear cells were collected two weeks after the last immunization for use as effector cells in the cytotoxic T lymphocyte assay and for the proliferation assay [32]. 

Results of methyl parathion assays involving effects on chromosomes have also been contradictory. For sister chromatid exchange, Waters et al. (1982) reported a positive response in Chinese hamster ovary cells only in the presence of metabolic activation system, while methyl parathion tested positive without a metabolic activation system in Chinese hamster V79 cells (Chen et al. 1981), cultured normal human lymphoid cells (Chen et al. 1981 Gomez-Arroyo et al. 1987 Sobti et al. 1982), and Burkitt s l5miphoma cells (Chen et al. 1981). Chen et al. (1981) found a significant dose-related increase in sister chromatid exchange in both hamster and human cultured cells, but dose-related cell cycle delays were less pronounced in human cell lines than in V79 cells. Negative results were obtained for chromosomal aberrations in human lymphocytes without a metabolic activation system (Kumar et al. 1993). 

Rodgers KE, Leung N, Imamura T, et al. 1986. Rapid in vitro screening assay for immunotoxic effects of organophosphorus and carbamate insecticides on the generation of cytotoxic T lymphocyte responses. Pestic Biochem Physiol 26 292-301. 

Gasiorowski, K., Brocos, B. DNA repair of hydrogen peroxide-induced damage in human lymphocytes in the presence of four antimutagens. A study with alkaline single cell gel electrophoresis (comet assay). Cellular Molecular Biology Letters, Vol.6, (2001), pp. 897-911, ISSN 1425-8153... 

Studies have demonstrated that one such method is to examine the effects of disinfectants on endogenous RNA-dependent DNA polymerase (i.e. reverse transcriptase) activity. In essence, HIV is an RNA virus after it enters a cell the RNA is converted to DNA under the influence of reverse transcriptase. The virus induces a cytopathic effect on T lymphocytes, and in the assay reverse transcriptase activity is determined after exposure to different concentrations of various disinfectants. However, it has been suggested that monitoring residual viral reverse transcriptase activity is not a satisfactory alternative to tests whereby infectious HIV can be detected in systems employing fresh human peripheral blood mononuclear cells. 

Eleven male volunteers aged 20-30 years ingested lead acetate for 49 days. PbB levels were kept at approximately 40 pg/dL. The frequency of chromosome aberrations was assayed after lymphocyte culture for 72 hours and found to be no different from that of 10 controls. The lymphocytes from lead-exposed subjects did show a higher mitotic activity (Bulsma and DeFrance 1976). 

Betti, C. and M. Nigro. 1996. The Comet assay for the evaluation of the genetic hazard of pollutants in cetaceans preliminary results on the genotoxic effects of methyl-mercury on the bottle-nosed dolphin (Tursiops truncatus) lymphocytes in vitro. Mar. Pollut. Bull. 32 545-548. 

Compounds that are not overtly myelotoxic may still selectively damage or destroy lymphocytes, which are the primary effectors and regulators of acquired immunity. This toxicity may result from the destruction of rapidly dividing cells by necrosis or apoptosis. A variety of methodologies are available for this purpose (e.g., colorimetric, flow cytometric assays). If the cells are viable (80% or greater), basic functionality could be determined by performing specific functional assays. 

Disparate effects on T-cell proliferative responses have been reported following exposure to JP-8. Significant suppression of T-cell proliferation is reported following either inhalation or dermal exposure to JP-8 [ 18,20,36], while the response is unaffected following either the oral or dermal exposure routes in other studies [66,71,72], These differences may be explained by variations in exposure routes and in assay methodology, as agents used to evaluate T-lymphocyte activation and proliferation were diverse and included Con A plus IL-2 [18,20], anti-CD3 [36], or Con A only [66,71,72],... 

Jackman, S.M., et al., DNA damage assessment by comet assay of human lymphocytes exposed to jet propulsion fuels, Environ, Mol. Mutagen., 40, 18, 2002. 

Ex vivo studies have revealed that trichothecenes can both inhibit and stimulate leukocyte function.12 For example, trichothecenes are toxic to alveolar macrophages,13 but drive differentiation of human myeloid leukemic cells.14 Dose-dependent decreases or increases in B- and T-cell mitogen responses are observable in lymphocytes from animals exposed to T-2 toxin, DON, or various macrocyclic trichothecenes these toxins similarly impair or enhance mitogen-induced lymphocyte proliferation in vitro.12 Rank order of inhibitor potency in rodent and human lymphocyte proliferation assays is Type D > Type A group > Type B group and is dependent on degree of acylation as well as of uptake and metabolism. 

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