Jack Gross

Studies on the radiobiological effect of 3H-thymidine on the DNA turnover in Landschütz ascites tumour cells

Abstract The radiobiological effect of Tritiated Thymidine ( 3 H-TDR) in Landschutz ascites tumor cells, was investigated in the following system. The cells were incubated in vitro with 3 H-TDR. The utilization of 3 H-TDR at various time intervals and after various levels of radioactivity was analysed by the addition of a second dose of 3 H-TDR and analysis of the incubation mixture for labeled nucleic acid and labeled precursor pool. Increasing the dose of 3 H-TDR above the level of 0.7 μc/10 8 cells resulted in a decreased uptake of 3 H-TDR by the cells. The inhibition of the uptake was proportional to the radioactivity of the 3 H-TDR in the initial dose. It was also observed that the 3 H-TDR caused a breakdown of DNA with the appearance of its label in the precursor pool. This effect increased with the time of exposure to the first radiation dose. It is activated only by the second 3 H-TDR dose. This effect is explained by the activation of nucleases.

Effect of Thyroid Hormone on Protein Biosynthesis by Cell-Free Systems of Liver.

Summary The microsomal system derived from the livers of thyroidectomized rats shows a markedly reduced ability to incorporate L-leucine-C14 into protein. This effect can be corrected by pretreatment of the thyroidectomized animal with triiodothyronine, but not with growth hormone.

Electron microscopic autoradiography of the metabolism of 125I in the thyroid gland

Twenty-four hours after the administration of I/sup 125/ to iodine- deficient mice, the autoradiographic localization of the isotope was determined at the electron microscopic level. Resolution appeared to approach 0.1 mu . ln addition to labeling in the colloid, intracellular vesicles containing I/sup 125/ were demonstrable. It is suggested that this appearance indicates absorption of colloid during the course of thyroid hormone secretion.

A Thermostable Cytotoxic Factor in Normal Human Serum Active Against Landschutz Ascites Tumor Cells.

Summary A heat stable factor (SF) in normal human serum which is cytotoxic to Landschutz ascites tumor cells has been described. The cytotoxic action requires the presence of human or rabbit complement but guinea pig complement is ineffective. The substance is found in the beta-globulin fraction and has characteristics similar to C′4 of human complement. It is selectively absorbed on human and mouse tumor cells and human placenta but not by normal human liver, kidney or heart. SF inhibits the action of heterologous antibody on ascites and HeLa cells. We are indebted to Dr. A. Rimon, Marcus Memorial Blood Bank Institute, Jaffa, for the Cohn fractions, and to Dr. Esther Tenenbaum of this Department for a generous supply of HeLa cells and Chang cells.

Sex hormone binding globulin (SHBG) in breast cancer: a correlation with obesity but not with estrogen receptor status

Plasma sex hormone binding globulin (SHBG) levels were determined in a group of 82 patients suffering from breast carcinoma with a known estrogen receptor status (ER). Overweight (greater than 20% of ideal weight) premenopausal patients had a significantly lower SHBG plasma level than their non-obese counterparts (43 pmol/ml vs 72.7 pmol/ml, P less than 0.001). No difference in plasma levels of SHBG was found between obese and non-obese postmenopausal patients. No correlation was found between SHBG levels and ER status either in non-obese premenopausal patients or in postmenopausal patients in general. Breast carcinoma patients had significantly higher SHBG plasma levels than a group of normal controls (57.9 pmol/ml vs 40.6 pmol/ml, P less than 0.01), but the stage of the disease did not influence the SHBG level within the breast carcinoma patients. Results of this study do not support a correlation between SHBG levels and ER status. SHBG plasma levels are significantly influenced by a patients weight, particularly in those who are premenopausal.

Purification and Partial Characterization of Mouse Hemopexin (Beta 2-III Globulin).

Summary A method for purification of mouse Beta 2-111 globulin is described. The purified protein is perchloric acid soluble and contains hexose, hexosamine and sialic acid. It is soluble in rivanol and binds hematin. It has a sedimentation constant of 4.3 S, indicating a molecular weight of about 65,000. It is suggested that this protein henceforth be called mouse hemopexin.

Complement-dependent lysis of Erhlich ascites tumor cells by human serum (ascitolysin) in lowered in cancer patients and raised in pregnant women

Normal human serum has been shown to contain IgM antibodies that are lytic to Ehrlich ascites tumor cells in the presence of complement. We call this activity ascitolysin (AL). Using a 51Cr release assay, the AL titers of 164 normal sera, 211 sera from patients with non-malignant disease, 62 sera from 25 pregnant women and 170 sera from cancer patients were estimated. The patient sera were taken preoperatively, and were assigned to the cancer or non-cancer group after histological diagnosis. In normals, higher titers were found in sera of A and O blood groups but not B and AB. The difference was due to a fraction absorbed by B red blood cells. Sera from untreated cancer patients showed significantly reduced titers when compared to normal, benign tumor, chronic and other non-malignant disease groups. In pregnancy, titers were positively correlated with duration and remained elevated for at least 6 weeks post partum. About 30% of AL activity was absorbed by the free galactose groups of agarose. This fraction was significantly lower in untreated cancer patients. Anti-T antigen antibodies do not contribute to AL levels. Galactophilic blocking factors were also found; eight times more frequently in cancer sera than in normals. The non-absorbed fraction was also lower in cancer sera. The data suggest that AL antibodies may be directed against human oncofetal antigens.

An Immunochemical Assay for Natural IgM Antibodies with an Affinity to Galactose and Whose Titer is Reduced in the Sera of Cancer Patients

Normal sera contain an IgM fraction which binds to free galactosyl groups of agarose. This fraction causes complement-dependent lysis of Ehrlich ascites tumor cells (EATC). Cancer sera show a much reduced titer of this lytic activity. In this paper we describe an immunochemical assay for these galactophilins (GALF). Agarose columns were immunoabsorbent and bound proteins were detected by labeled antibody to human IgM. All 157 normal sera contained GALF. The serum GALF concentrations of normal sera were linearly correlated to the serum cytolytic titers. However, EATC absorbed only 15% of normal serum GALF. The titers in normal females are higher than in males. The titers in 147 nonmalignant chronic disease patients were lower than the normals only in women over 40 years of age. The sera of 138 cancer patients, taken before any therapy, were significantly lower than the corresponding normal or chronic disease controls. Lymphoproliferative neoplasms were associated with the lowest titers while melanoma sera showed normal titers. It is likely that GALF is bound to tumor associated antigens with free galactosyl groups. These are on the cell surface and/or are shed into the circulation. GALF titration may prove useful in following treatment efficacy in individual cancer patients.

Inherited Disorders of Thyroid Hormone Action

Disorders of thyroid hormone action have only been characterized by resistance to thyroid hormone (THR). This is manifest by a normal or high circulating level of thyroid hormones with an inappropriate response of the target tissues, either in terms of metabolic activity and/or TSH secretion. There are a number of comprehensive reviews (1,2) that have dealt with the subject up to 1981. I have reviewed the literature to date to try and obtain further insight into the types, frequencies, and underlying mechanisms of these disorders. Because of the small number of cases reported, I have included sporadic, as well as inherited cases. I will also mention two animal models of inherited thyroid hormone resistance.

Vitamin B12 content of cells of the blood, bone marrow and liver of the rat.

Summary Vit B12 content was determined microbiologically in different cellular elements of the rat. The highest concentration was found in liver cells. The vitamin B12 content of nucleated bone marrow cells and circulating leukocytes was of the same magnitude, except for the nucleated cells of the skull which had a higher concentration than the other marrow sites. The lowest concentration of vit B12 was found in the red cells.