Biomedical subjects
Publications and source records attributed to H F Cheng.
A tumor-associated protein was found in tissue derived from an X-irradiation-induced adenocarcinoma in the small bowel of the rat. The protein was associated with the cell membranes of the tumor tissue. It shared common antigenic determinants both with a rat fetal protein and a perchloric acid-soluble protein isolated from the serum of the tumor-bearing rat.
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A heritable alteration in the natural immunity as measured by changes in the natural killer (NK) cell activities of peripheral blood lymphoid-cells was found to occur in rats upon an in utero exposure to iodine-131. The model that was employed for the measurements consisted of Fischer F344 inbred rats exposed to iodine-131 (sodium) during their 16th to 18th day of gestation. The natural immunity of the animals was evaluated by determining the NK cell activities of peripheral blood lymphoid cells of the offsprings when they reached 2 months of age. Immediately following determination of the natural immunity, brother and sister matings were carried out for evolution of the families. Study of these pedigrees revealed an impairment in the natural immunity to persist through two generations (F1, and F2) of the male animals. The hematological profiles of the animals suggest that the insult may alter the numbers of red and white blood cells in the succeeding generations, but has little noticeable effect upon the percentage of lymphocytes. The interpretation of the results indicate that a perinatal insult by iodine-131 during late gestation can result in both somatic and germ cell changes in the immunological system. Thus, there appears to be a genealogical memory to an in utero radionuclide insult which may adversely affect the offspring's immunological competency to respond to subsequent insults.
A study was recently completed which indicated the first generation of adult rats that had been exposed perinatally to iodine-131 possessed peripheral blood lymphoid-cells capable of expressing cytotoxicity towards cultured small bowel adenocarcinoma target cells, i.e., active antitumor cell-mediated immunity (CMI). The results gathered during the current investigation suggest that such animals similarly express anti-tumor antibody-dependent cell-mediated immunity (ADCC). The animal model employed consisted of Fisher F344 inbred rats exposed to iodine-131 (sodium) during their 16th to 18th day of gestation, and at an interval of two months post-partum when the offsprings had matured into adults, they and their mothers were evaluated for the presence of serum components capable of expressing ADCC activities toward X-ray induced small bowel adenocarcinoma target cells. Significant ADCC activities were found to be expressed by the offspring while no analogous immunological responses could be detected in the serum of the mothers. This lack of maternal ADCC activity suggests the existence of a biological block developing during pregnancy resulting in the mother being immunological nonresponsive to carcinogenic insults. One serum component present in the offspring identified as being responsible for initiating ADCC was an immunoglobulin of the IgG class as based upon its physical characteristics: solubility, molecular weight, and reactivity with anti-immunoglobulins, pepsin, and protein A. The interpretation of these findings is that perinatal exposure to radioiodine results in the development of cells having foreign-like properties in the offspring which are recognized by the animal's immune system, thus resulting in detectable antitumor CMI and ADCC immune responses.
Studies were undertaken with the intent to establish the degree of risk experienced by a mother and her immediate offspring in developing gastrointestinal cancer following exposure to iodine-131 during pregnancy. An indirect approach in the identification of tumor induction for risk determination was utilized in this study which relied upon the measurement of antitumor cell-mediated immunity (CMI) occurring in the host following exposure to the radionuclide. Fischer F344 inbred pregnant rats were selected as the animal model, and the radionuclide exposure was accomplished by a single intraperitoneal administration of iodine-131 [Na131] at the stage of 16-18 days of pregnancy; then at two months postpartum, the dams and pups were evaluated for the capacity of their peripheral blood lymphoid cells to express specific cytotoxic responses towards target cells consisting of cultured X-ray induced rat small bowel adenocarcinoma cells. The results indicate that an antitumor immunity was induced in the pups upon such a prenatal exposure, while none could be detected existing in their mothers. In addition, there appeared to be a possible sex or hormonal component as a preliminary consideration of the data suggested the male offspring were approximately 1.7 times more immunoresponsive to the perinatal insult. Threshold detection level for detecting such responses to the iodine-131 was found to be in the range of a 9.25 kBq (250 nCi) quantity of exposure. The implication of these preliminary findings based upon such indirect measurements is that the first generation may be at an increased risk to gastrointestinal cancer following peritanal exposure to iodine-131 in the later stage of pregnancy.