Lymphocyte abnormal numbers

Immunological abnormalities were reported in 23 adults in Woburn, Massachusetts, who were exposed to contaminated well water and who were family members of children with leukemia (Byers et al. 1988). These immunological abnormalities, tested for 5 years after well closure, included persistent lymphocytosis, increased numbers of T-lymphocytes, and depressed helper suppressor T-cell ratio. Auto-antibodies, particularly anti-nuclear antibodies, were detected in 11 of 23 adults tested. This study is limited by the possible bias in identifying risk factors for immunological abnormalities in a small, nonpopulation-based group identified by leukemia types. Other limitations of this study are described in Section 2.2.2.8. A study of 356 residents of Tucson, Arizona, who were exposed to trichloroethylene (6-500 ppb) and other chemicals in well water drawn from the Santa Cmz aquifer found increased frequencies of 10 systemic lupus erythematosus symptoms, 5 (arthritis, Raynaud s phenomenon, malar rash, skin lesions related to sun exposure, seizure or convulsions) of which were statistically significant (Kilbum and Warshaw 1992). 

Purine nucleoside phosphorylase (PNP) deficiency engenders a combined immunodeficiency and neurologic abnormalities and is usually fatal in childhood (G4). Patients with PNP deficiency have profound lymphopenia and a small thymus with poorly formed Hassall corpuscles. Lymphocyte enumeration shows markedly decreased numbers of T cells and T-cell subsets, with normal percentages of B cells. Point mutations and a splicing mutation have been identified in some PNP-deficient patients (H4). 

In patients infected with HIV, many nonspecific and certain specific cellular immune functions can be shown to be altered or decreased, and a number of seemingly healthy individuals may exhibit marked immunological abnormalities without evidence of clinical illness. As the individual begins to exhibit clinical symptoms associated with AIDS, the abnormalities in the immune system become more extreme. A factor that complicates the study of HIV-induced immunosuppression is that many of the infections patients develop may themselves induce marked changes in the immune system. For this reason, it has been difficult to dissociate the fundamental changes associated with prolonged HIV infection from epiphenomena caused by other infections. One basic defect in the immune system of HIV-infected patients has, however, been elucidated. This is the loss of function and ultimate destruction of a proportion of T lymphocytes. 

More recently, Merz et have studied the circulating lymphocytes of humans experimentally exposed to ozone at 0.5 ppm for 6-10 h. A statistically significant increase in the number of minor chromosomal abnormalities (not breaks) was observed it reached a peak about 2 weeks after exposure and later returned to normal. This delay in the development of chromosomal abnormalities observed after ozone exposure in both hamsters and humans differs from that observed in human radiation studies, in which aberrations tend to remain roughly constant over 3-4 weeks. This raises the possibility that the ozone-induced abnormality is related to a postreplication repair process. 

A continuation of this line of studies for 6 days to 23 weeks at 300 ppm showed continued decreases in numbers of mature B- and T-lymphocytes produced in the bone marrow, spleen, and thymus (Rozen and Snyder 1985). Abnormalities of humoral and cell-mediated immune responses following benzene exposure are presumably caused by a defect in the lymphoid stem cell precursors of both T- and B-lymphocytes. Bone marrow cellularity increased 3-fold, and the number of thymic T-cells increased 15-fold in benzene-exposed mice between the 6th and the 30th exposure. No corresponding increase in splenic cells was noted. The marked increase in the numbers of cells in bone marrow and thymus was interpreted by the authors to indicate a compensatory proliferation in these cell lines in response to... 

Cytogenetic analyses for chromosomal aberrations were carried out on cells from mice (1) and Chinese hamsters (12) created with BZ and on human peripheral lymphocytes (1) created in vitro. It was reported chat BZ did not induce translocations and did not Increase the number of abnormal metaphases in spermatocytes from male mice. 

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