fgr is a member of the protein kinase oncogene family and was found to have the highest homology to yes gene among the members of the family. Using a v-yes probe, a molecular clone of human c-fgr locus was isolated from a genomic library. Nucleotide sequence determination revealed that the actin gene-like sequence found in v-fgr gene was absent at the corresponding position of the c-fgr gene. Thus, the v-fgr gene product is considered to be a tri-chimeric gene product consisting of viral gag gene and two distinct cellular genes, actin gene and the proto-fgr gene.

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No consistent chromosome abnormalities have been reported so far in T-cell lymphoma-leukemia. We report here two children suffering from T-cell acute lymphoblastic leukemia (ALL) with t(11;14) (q13;p11). Even though the breakpoints we claim are different from those in a recent report, we believe that their cases and ours have the same abnormality and that patients with this abnormality constitute a distinct subgroup of T-cell ALL positive for sheep erythrocyte receptor (E⁺) in children.

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Japanese xeroderma pigmentosum sib patients XP58TO and XP59TO were assigned to complementation group D on the basis of cell hybridization studies. Ultraviolet and 4-nitroquinoline-1-oxide hypersensitivity and reduced unscheduled DNA synthesis of cells of these XP patients were also characteristic of authentic group-D cells. The patients have not yet developed either apparent neuro-mental abnormalities or skin cancers.

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The effect of gastrectomy and duodenal reflux on gastric carcinogenesis was studied because gastrectomized patients may be considered at “high risk” for the development of gastric stump cancer. Wistar rats received N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (83mg/liter) ad libitum in the drinking water for either four, eight, or twelve weeks. A control group received tap water. After MNNG administration animals were antrectomized. Antrectomy was not performed in a control group. Bowel continuity was restored either with a Billroth II (BIL) or with a ROUX en Y (ROUX) procedure. Duodenogastric reflux is possible after the BIL but not after the ROUX procedure. Eight months after the beginning of the experiment the stomachs of the animals were studied. In both operated and unoperated animals, the number of cancers observed was significantly related to the duration of MNNG administration. Animals receiving MNNG plus the BIL procedure had a significantly higher number of anastomotic cancers than the ROUX animals, indicating that duodenogastric reflux played a promotional role in gastric carcinogenesis. Three BIL gastrectomized rats not receiving the carcinogen had an adenocarcinoma on the anastomotic line further emphasizing the risk attached to the duodeno-gastric reflux.

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Of the three metabolic oxidation pathways of N-nitrosodibutylamine (NDBA) demonstrated in vivo, ω oxidation is responsible for the induction of bladder tumors, while ω-1 and ω-2 oxidations are considered to be associated with the induction of liver tumors by NDBA. The metabolic fate of the following five NDBA derivatives was investigated in the rat in order to elucidate further the metabolic characteristics of NDBA in relation to its hepatocarcinogenic activity: N-nitroso-N-(3-hydroxybutyl)butylamine (NHBBA-3), N-nitroso-N-(3-oxobutyl)butylamine (NOBBA-3), N-nitroso-N-(2-hydroxybutyl) butylamine (NHBBA-2) and N-nitroso-N-(2-oxobutyl)butylamine (NOBBA-2), which are involved in the ω-1 and ω-2 oxidation pathways of NDBA, and N-nitroso-N-(2-oxopropyl)butylamine (NOPBA), a minor urinary metabolite of NDBA. By characterization of the urinary metabolites, NHBBA-3 and NHBBA-2, primary metabolites of NDBA, were shown to undergo further oxidative metabolic transformation via NOBBA-3 and NOBBA-2, respectively, although conjugation with glucuronic acid to afford the glucuronides was demonstrated to be their principal metabolic pathway. The principal urinary metabolite of NOBBA-2 as well as NOBBA-3 was N-nitroso-N-(carboxymethyl)butylamine, while reduction of the oxo group followed by glucuronidation was found to be a minor metabolic pathway. The glucuronide of N-nitroso-N-(2-hydroxypropyl)butylamine was the principal metabolite of NOPBA, N-nitroso-N-(carboxymethyl)butylamine being a secondary metabolite. The hepatocarcinogenic activity of the three oxo compounds (NOBBA-3, NOBBA-2 and NOPBA) in relation to that of NDBA is discussed from the metabolic point of view.

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In order to compare the extents of metabolic α-hydroxylation of the two alkyl groups in unsymmetrical N-nitrosodialkylamines, N-nitroso-N-alkylbutylamines (alkyl=methyl, ethyl, propyl, butyl, and amyl) were incubated with liver microsomes prepared from phenobarbital- or polychlorinated biphenyl (PCB)-treated and untreated rats, and aldehydes produced by the α-hydroxylation were determined quantitatively. Although an increased production of aldehydes was observed with the induced microsomes compared with the non-induced microsomes, no marked differences were noted between the two alkyl groups of these unsymmetric nitrosodialkylamines in regard to the extent of α-hydroxylation with the exception of N-nitroso-N-methylbutylamine (NMBA). The amount of aldehydes produced from these nitrosamines increased with elongation of the alkyl chain, amounting to 10-30% of the compounds incubated, and the recovery in the incubation (total aldehyde+nitrosamine recovered) was found to be more than 90%, indicating that α-hydroxylation is the principal oxidative metabolic pathway of the nitrosamines in vitro. The microsomal α-hydroxylation was inhibited by dimethyl sulfoxide and the extent of the hydroxylation was shown to be positively correlated with the mutagenic potency of the nitrosamines. Based on the mutagenic behavior of NMBA tested on Salmonella typhimurium TA1535 and Escherichia coli WP2 hcr^- and the extent of the formation of formaldehyde and butyraldehyde from NMBA in the presence of the induced microsomes and S9 mix, it was concluded that NMBA acts as both a methylating and a butylating agent.

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The concentration of N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), which is the major metabolite of the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), was measured in the urine, thymus, liver, kidney, and bladder of rats orally administered with BBN. Since BCPN is a carboxylic acid, it forms an ester with 9-anthryldiazomethane (ADAM), which is a fluorescent labeling agent highly sensitive to carboxylic acids. Thus, BCPN and ADAM were reacted at 40°for 1hr, and the resulting ester was separated and measured by high-performance liquid chromatography (HPLC) with a reverse-phase type column. The range of measurement was 0 to 40 μg/ml, and the coefficient of variation (CV) was 3.8%. When 0.025% BBN was given orally to rats in tap water, the BCPN concentration in the urine was very high at 220 μg/ml, while it was 0.15μg/100mg in the wet tissues of the thymus, 0.35μg/100mg in the liver, 0.40μg/100mg in the kidney, and 1.2μg/100mg in the bladder. The BCPN concentration in the bladder, in which tumors are induced by the administration of BBN, was thus higher than those in the other organs.

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In order to better understand the carcinogenic process, a comparative study was undertaken of the association of nitrosamine-derived radioactivity with nuclear and mitochondrial DNA isolated from tumor-susceptible and non-tumor-susceptible tissues of two strains of mice with different susceptibilities to tumor induction by dimethylnitrosamine (DMN) or diethylnitrosamine (DEN). A single dose of either [¹⁴C]-DMN or [¹⁴C]DEN was administered by intragastric intubation to young adult male RFM or BALB/c mice. The DNA isolated from the mitochondrial fraction of tumorsusceptible tissues bound several times (10 to 90) more nitrosamine than the nuclear DNA. These results suggest that mitochondrial DNA may be a target in the carcinogenic process induced by nitrosamine compounds.

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The total post-heparin lipolytic activity (PHLA) and hepatic triglyceride lipase (HTGL) and lipoprotein lipase (LPL) activities in post-heparin plasma of patients with various cancers were measured. In patients with cancers, PHLA was similar to that of controls, but the HTGL activity was decreased and the LPL activity was increased. Thus, in cancer patients the ratios of HTGL to PIMA were lower, and the ratios of LPL to PHLA were higher than in controls. No correlation was found between the plasma lipid level and HTGL or LPL activity.

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Neoplastic angioendotheliosis (NAE) is a rare disease characterized by the occlusion of small vessels by apparently neoplastic medium-sized cells. The origin of these cells remains undetermined, mainly because the diagnosis in most of these cases has been made on autopsy. This report describes a case of NAE from whom a biopsy specim en was obtained and studied immunohistologically. The cells occluding small vessels of this patient bear B cell markers such as monoclonal immunoglobulin (μ, λ), Leul4, B1, OKB2, and Dako-PanB, whereas they do not react with antibodies against δ- and κ-chain of immunoglobulin (Ig), or antibodies against markers of T cells, myelomonocytic cells and endothelial cells. These results show clearly that the cells occluding the small vessels of this patient are neoplastic and of B cell lineage. This is the first case of NAE in whom the neoplastic cells in the blood vessels have been proved to be of lymphocytic lineage.

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An antitumor principle (SAGP) has been purified from cell-free crude extract (CE) of group A Streptococcus hemolyticus, Su strain. The antitumor activity of each fraction was evaluated by measuring the in vitro growth inhibitory effect on transformed hamster embryonic lung cells (THEL). CE was subjected to thermal treatment, streptomycin precipitation, ammonium sulfate precipitation, and chromatography on octyl-Sepharose CL-4B, DEAE-cellulose, and Sephadex G-200 in that order. The active fraction from the last chromatography was dialyzed against distilled water. The resulting precipitate was removed and the supernatant was lyophilized (SAGP). SAGP is a homogeneous glycoprotein as judged by polyacrylamide gel electrophoresis, gel filtration, immunodiffusion, and PAS-staining. The molecular weight of SAGP was determined to be 140, 000 to 150, 000 by the gel filtration technique. SAGP is composed of subunits, each of which has a molecular weight of about 50, 000. The isoelectric point of SAGP is 4.3. Amino acid analysis revealed an abundance of aspartic and glutamic acid residues in SAGP. The 50% growth inhibitory dose of SAGP on THEL was 0.062μg/ml. Intraperitoneal administration of SAGP (20mg/kg/day×4) to ICR mice bearing Ehrlich ascites carcinoma cells increased their life span to 254% of the control.

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The antiviral and anticellular activities of recombinant human interferon-γ (ReIFN-γ) were compared with those of natural human interferon-γ (IFN-γ), natural human interferon-α (IFN-α), and recombinant human interferon-β (ReIFN-β). ReIFN-γ and IFN-γ induced the antiviral state in FL cells against Sindbis virus more rapidly than IFN-α or ReIFN-β. The antiviral state induced by a short exposure time to IFN-γ declined rapidly after the removal of IFN-γ and the incubation of FL cells in fresh medium, whereas that induced by ReIFN-γ was persistent. However, other characteristics of the antiviral activity of ReIFN-γ were shown to be very similar to those of IFN-γ (e.g., stability at 56°or pH 2.0, and neutralization by anti-IFN serum). The anticellular spectrum of ReIFN-γ or IFN-γ against 26 human cell lines differed in some respects from that of IFN-α or ReIFN-β, since ReIFN-γ and IFN-γ were more effective at inhibiting the growth of human carcinoma or sarcoma cell lines. The IC₅₀ (IFN concentration required for 50% growth inhibition) values of ReIFN-γ were several times smaller than those of IFN-γ in all cell lines sensitive to both IFNs. ReIFN-γ and IFN-γ, but not IFN-α or ReIFN-β, were cytotoxic against HeLa S₃ cells. These cytotoxicities of both IFNs were inactivated by treatment at 56°or pH 2.0 and by anti-ReIFN-γ serum. These results indicate that the characteristics of antiviral and anticellular activities of ReIFN-γ are somewhat different from those of other IFNs including IFN-γ.

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This retrospective analysis describes the reactivity of several monoclonal antibodies (MoAbs) which detect myelomonocytic antigens of the cells of 182 leukemias. These leukemias were assigned to definite subtypes of lymphocytic and myelo(mono)-cytic leukemias on the basis of standard leukemia phenotyping using morphological, cytochemical, isoenzymatic and mainly immunological criteria. The MoAb MCS-2 was negative in all cases of lymphocytic leukemia, whereas two of the three other commonly used “myeloid MoAbs” MCS-1, OKM-1 and 1/12/13 showed positivity in B-chronic lymphocytic leukemia (B-CLL), B-lymphoma (MCS-1), T-acute lymphoblastic leukemia (T-ALL) and Sézary syndrome (OKM-1). MCS-2 was positive in all samples of acute myelomonoblastic leukemia (AMMoL), chronic myelocytic leukemia (CML) and CML-myeloid blast crisis, which was not the case for MCS-1, OKM-1, or 1/ 12/13. In 14 cases (11 acute myeloblastic leukemia (AML), 3 CML-myeloid blast crisis) where MCS-2 was positive and one or all of the three other MoAbs were negative, the cells were mainly Ia-positive and peroxidase-negative. MCS-2 is a diagnostically important MoAb in the routine leukemia phenotyping of myelomonocytic leukemias. After having tested a large number of normal and malignant specimens, we would like to term MCS-2 a “pan-myeloid MoAb” reacting with the myelomonocytic cell lineage from the earliest myeloblast to granulocytes and monocytes.

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