Small F chromosome in myelo- and lymphoproliferative diseases

A deleted F group chromosome was observed in five patients with myeloproliferative and lymphoproliferative diseases. Three patients had a small F chromosome with both arms deleted, 19p-q-. Each of these patients had a different disease, acute myelomonocytic leukemia (AMML), lymphosarcoma (LSA), and erythroleukemia, respectively. One patient had a hyperplastic marrow and erythroid hyperplasia for a year prior to the development of acute myelogenous leukemia (AML), and had a small F chromosome with del(20)(q12) which is similar to the small F chromosome reported in patients with polycythemia vera. No banding studies were available on one patient with sideroblastic anemia and possible erythroleukemia. These cytogenetic findings lead us to believe that: (1) there is a high incidence of F chromosome abnormalities in cases with abnormal erythropoiesis; (2) erythroid diseases may be predisposed to the small F chromosome abnormality, which is enhanced by treatment, such as irradiation; and (3) the cells with a small F chromosome are rather stable and can gradually replace cytogenetically normal cells without affecting the clinical course of the diseases, and it is the emergence of additional chromosomal abnormalities in these cells which signal a poor prognosis.     

Effect of phenacetin and N-alkylacetanilides on N-2-fluorenylacetamide hepatocarcinogenesis

Phenacetin, N-methylacetanilide and N-ethylacetanilide prevented N-2-fluorenylacetamide hepatocarcinogenesis in F344 strain rats. Phenacetin was most effective followed by N-ethylacetanilide. Phenacetin was not carcinogenic when fed at 0.8% level for 16 weeks followed by control diet for another 10 weeks.     

Butyrate prevents Harvey Sarcoma virus focus formation but permits oncogene expression

Since butyrate inhibits DNA synthesis and cell growth, we adapted NIH 3T3 cells to grow in butyrate to study its effects on retroviral cell transformation. In cultures of butyrate-adapted NIH 3T3 cells infected with Harvey Sarcoma Virus, no foci were formed; however, there was evidence of retroviral replication, and the P21 oncogene product was demonstrated by immunofluorescence in its characteristic localization beneath the cytoplasmic membrane of single cells and pairs of cells. When the butyrate was removed, these cells proliferated to form foci. Butyrate therefore does not prevent oncogene expression but does reversibly inhibit focus formation.     

Formation of metastasis by human breast carcinoma cells (MCF-7) in nude mice

MCF-7 cells, a human breast carcinoma line, forms tumors when injected into athymic nude mice. These tumors are able to metastasize to lungs, liver and spleen. 17 beta-estradiol treatment increases both the growth rate and frequency of metastases. Castration or diabetes prevents metastasis formation, but treatment with estrogen or insulin restores the metastasizing capacity. MCF-7 cells secrete into the culture media collagenases able to lyse types I and IV collagens. Estrogen or insulin addition to the culture enhances collagenase production. Attention is called to the coexistence of enhancement in collagenase production and metastasis formation.     

Chromatin conformation during cell differentiation of human myeloid leukemia cells.

A novel human promyelocytic leukemia cell line (HL-60) has been shown to form terminally differentiated granulocytes in the presence of dimethyl-sulfoxide (DMSO), some other chemicals, or colony stimulating factor. Compared to chromatin from HL-60 cells, chromatin from DMSO treated HL-60 cells showed an enrichment in low temperature melting material. The decrease in thermostability of chromatin from HL-60 cells after DMSO treatment is similar to the shift in thermostability of chromatin from human lymphocytes after stimulation with phytohemagglutinin (PHA). These results suggest that changes in the thermostability of chromatin may not be specific for cell differentiation or PHA stimulation.     

Influence of exogenous estrogen on oocytic depletion induced by 7,12-Dimethylbenz[a]anthracene in mice

The influence of exogenous estrogen on the action of 7,12-Dimethylbenz[a]anthracene (DMBA) on ovaries of Swiss albino mouse has been studied. DMBA elicits the depletion of oocytes; but concomitant administration of estrogen with DMBA reduces this loss of oocytic population significantly.     

A comparative cytogenetic study of melphalan-sensitive and -resistant murine L1210 leukemia cells

A cytogenetic analysis of melphalan-sensitive and -resistant murine L1210 leukemia cells maintained in vivo indicated that the drug-resistant tumor had a modal number of 40 chromosomes while the sensitive tumor possessed a mode of 41 chromosomes. Two marker chromosomes were present in both the sensitive and the resistant tumors. One was of medium length with secondary constrictions, and the other was a minute chromosome. A single in vitro exposure of the sensitive tumor cells to a cytotoxic concentration of melphalan was not accompanied by a change in modal number but resulted in chromatid exchange. No alterations were found in resistant tumor cells which were exposed to the same drug concentration. However, exposure of resistant tumor cells to higher doses of melphalan resulted in chromatid breaks, chromatid gaps and the formation of acentric chromosomes. The resistant tumor, transplanted once without drug injection, maintained a sharp mode of 40 chromosomes.     

Alterations in electrophysiology of cultured BALBcfC3H mouse mammary epithelium associated with neoplastic transformation

Mammary tumor virus and neoplastic transformation affect prolactin-modulated electrophysiology of mouse mammary epithelium in vitro. Trans-epithelial resistances of both prelactating and neoplastic $\text{BALB}\text{cfC3H}$ mouse mammary epithelial cell cultures are lower than those seen in $\text{BALB}\text{c}$ pre-lactating cell cultures. Unlike the response to prolactin in $\text{BALB}\text{c}$ cultures, there are no effects of this hormone on transepithelial potential difference or resistance of $\text{BALB}\text{cfC3H}$ prelactating or neoplastic cultures. However, prolactin significantly increases short-circuit current in both $\text{BALB}\text{c}$ and $\text{BALB}\text{cfC3H}$ prelactating cell cultures and in $\text{BALB}\text{cfC3H}$ neoplastic cell cultures. The response of tumor cell cultures suggests that pregnancy-independent mouse mammary epithelium may not be entirely refractory to prolactin.     

Amino-α-carbolines as mutagenic agents in cigarette smoke condensate

Two mutagenic agents, 2-amino-9H-pyrido[2,3-b]indole and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (amino-α-carbolines) have been isolated from cigarette smoke condensate for this study. The former agent varied in amounts from a low of 25 ng/cigarette in the smoke of flue-cured tobacco, to a high of 258 ng/cigarette in a cigarette of Japanese domestic variety. The latter ranged in amounts from 9 to 37 ng/cigarette. The contents of these mutagens in the smoke condensate were positively related to an increase in mutagenic activity of Salmonella typhimurium TA 98.     

Tumor markers: value and limitations in the management of cancer patients

Sixteen tumor markers are reviewed, and measured to the ideal: produced by the tumor cell alone absent in health and in benign disease present in all patients with a given malignancy level in the blood representative of tumor mass detectable in occult disease. The only marker that approaches the ideal is human chorionic gonadotropin (HCG) in gestational trophoblastic tumors. In this malignancy, the HCG level suggests the diagnosis and stage, confirms response to therapy, and predicts relapse. The three most widely used and intensely studied tumor markers are carcinoembryonic antigen (CEA), alphafetoprotein (AFP), and HCG. CEA cannot be used in screening for cancer, but in carcinoma of the colon its elevation preoperatively increases the likelihood of advanced disease and postoperative recurrence. Postoperatively, elevated titers are often but not invariably associated with recurrent disease. AFP and HCG are useful in the management of nonseminomatous germ cell testicular tumors. Like CEA, they cannot be used for screening. They are more likely to be increased with advancing stage, and after therapy rising levels almost always mean recurrent disease. Some markers are valuable in specific circumstances, such as calcitonin in screening for familial medullary carcinoma of the thyroid. In multiple myeloma, immunoglobulins are useful in determining the tumor mass and response to therapy. In neuroblastoma, catecholamine metabolites are useful primarily in making the diagnosis. In some malignancies, the absence of effective therapy lowers the value of the marker, as for AFP in hepatoma. The remaining markers are too unreliable or too little studied to be useful in the management of an individual patient with cancer. The purpose of this paper is to provide the clinician with an understanding of the limitations of the present tumor markers that will lead to wiser use of the tests, and to provide standards to which future tumor markers should be measured.     

Effects of 12-O-tetradecanoyl phorbol-13-acetate and epidermal growth factor on the proliferation of human mutant fibroblasts in vitro

Cultures of skin fibroblasts (SF) from individuals with hereditary adenomatosis of the colon and rectum (ACR) and from normal individuals were exposed to 12-O-tetradecanoyl phorbol-13-acetate (TPA) (0.5–100 ng/ml), and epidermal growth factor (EGF) (0.01–10.0 ng/ml) at both low and high cell densities. Cell proliferation of low density cultures (4.75 × 10³ cells/cm²) was inhibited by TPA, while cell proliferation of high density cultures (6 × 10⁴ cells/cm²) was stimulated by TPA. EGF was mitogenic at both cell densities of normal and ACR-SF cultures. TPA and EGF each produced characteristic changes in the morphology of ACR-SF colonies. The results suggest that EGF and TPA may share only 1 class of receptors, and that TPA may be used to monitor cancer progression.     

Quantitation of differences between spontaneous and induced liver tumors in mice with an automated image analyzer

Spontaneous hepatocellular neoplasms of B6C3F1 mice (basophilic neoplasms) as well as those induced with the herbicide Nitrofen (eosinophilic neoplasms) were observed with an image analyzing computer to determine if quantifiable morphologic differences existed between them. Several morphologic parameters were measured on 5 liver sections from each of the following groups: (a) unexposed control liver; (b) non-trabecular basophilic neoplasms; (c) trabecular basophilic neoplasms; (d) small well circumscribed eosinophilic neoplasms; and large irregular eosinophilic neoplasms without (e) and with (f) pulmonary metastases. The total number of hepatocytes per unit area was significantly smaller in the eosinophilic neoplasms than in the basophilic neoplasms or the controls. This was the result of a greatly increased cell cross-sectional area in the eosinophilic neoplasms, caused predominantly by a larger cytoplasmic cross-sectional area. Nuclear cytoplasmic ratios of cells in eosinophilic neoplasms were lower than in the other groups for this reason. This demonstrates that quantitative morphologic differences exist between the spontaneous and induced neoplasms, which supports the conclusion that Nitrofen is a true carcinogen, and not a promoting agent.     

Hepatic vitamin A status of rats during feeding of the hepatocarcinogen 2-aminoanthraquinone

Dietary administration of the dyestuff intermediate 2-aminoanthraquinone (AAQ) at a 2% level for periods of 2, 4, 8 or 12 weeks decreased the total liver vitamin A significantly (P < 0.001) at all time periods in both male and female rats, compared to controls and pair-fed controls, respectively. A decrease in the body weights of AAQ-fed rats was much more pronounced in the females than male rats.     

125I interstitial brachytherapy for primary malignant brain tumors: technical aspects of treatment planning and implantation methods

Use of interstitial radiation holds promise in the treatment of primary malignant brain tumors, but optimal technical factors have yet to be determined. We have developed a method of precise CT directed stereotactic placement of radioactive sources in a predetermined target volume. We use low activity (1-2 millicurie/speed) sources of 125I loaded in silastic catheters, which are positioned in a parallel array in the target. Positioning of such multiple sources toward the periphery of the volume enhances achievable dose homogeneity. Seeds of various activities can be differentially loaded into each catheter and the catheters can be positioned at various radii from the central target so that the treated volume corresponds to the identified (often irregular) target volume. Although the implant is designed to be permanent, the sources can be removed easily in a second procedure.     

Prevalence of HTLV-specific antibodies in Surinam emigrants to the Netherlands

Sera of 98 participants in a methadone maintenance programme, all recent Surinam emigrants to the Netherlands, were examined for antibodies to disrupted HTLV using the ELISA technique. Twelve per cent of the donors possessed HTLV-specific antibodies with a range of titre from 41 to 20,000. Sera of 26 control Dutch drug users lacked such antibodies with the exception of one female who subsequently was found to reside with a Surinam male. Intravenous drug use was not a factor in these studies. These data indicate that HTLV circulates within the Surinam community in the Netherlands. More broadly, these results show that the region of the Caribbean endemic for HTLV extends as far south as Surinam. Furthermore, an antibody prevalence of 12% for clinically healthy donors with non-malignant disease suggests that the Caribbean has an incidence of HTLV infection approaching, if not equal to, that of southwestern Japan.