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Biomedical subjects

K Yokoro

Publications and source records attributed to K Yokoro.

At least 73 records · Page 4Linked to original sources

Induction of hepatic tumors by diethylstilbestrol alone or in synergism with n-nitrosobutylurea in castrated male WF rats.

Inbred male WF rats were castrated at 40 days of age and divided into 5 groups. Group I was given no further treatment. Groups III, IV, and V received pellet implants of 5.0 mg diethylstilbestrol (DES) concurrently with castration. At 50-55 days of age, groups II, IV, and V were given drinking water containing 5.0 mg N-nitrosobutylurea (NBU) per day for 30 days (subthreshold dose). At the termination of NBU treatment, group V further received daily sc injections of 2-bromoergocryptine (CB-154; 0.4 mg/100 g body wt) four times a week throughout the experiment. None of castrated rats or rats castrated and treated with NBU alone developed hepatic tumors (HT) and pituitary tumors (PT). Incidences of HT and PT in groups III, IV, and V were 4/9 (44%) and 7/9 (78%), 15/17 (88%) and 12/17 (71%), and 17/20 (85%) and 4/20 (20%), respectively. The treatment of DES alone resulted in the concurrent development of HT and PT in castrated male rats (group III), and further NBU treatment significantly increased the incidence of HT (group IV). CB-154 treatment did not change the incidence of HT, the number of HT per rat, and the liver weight, although it significantly reduced the incidence of PT, the pituitary weight, and the serum prolactin level in castrated male rats given DES and NBU (group V). These results indicate that DES itself had a direct carcinogenic effect on the liver; this effect was not mediated by prolactin, and NBU increased the effect of DES in this process.

Animals↗

Suppression of diethylstilbestrol and N-nitrosobutylurea-induced mammary and pituitary tumorigenesis in rats by prolonged treatment with 2-bromoergocryptine.

Inbred male W/Fu rats were castrated at 40 days of age (24) and divided into five groups. Group I was given no further treatment. Groups II, IV, and V received pellet implants of 5.0 mg diethylstilbestrol (DES) concurrently with the castration. At 50 to 55 days of age, Groups II, IV, and V were given drinking water containing 5.0 mg N-nitrosobutylurea (NBU)/day for 30 days. This amount does not induce mammary tumors (MTs) in castrated male rats (24) or in female rats (31). At the termination of NBU treatment, Group V received further daily s.c. injections of 2-bromoergocryptine (CB-154; 0.4 mg/100 g body weight) four times/week throughout the experiment. None of the castrated rats or rats castrated and treated with NBU alone developed MT or pituitary tumors (PTs). Incidences of MT and PT in Groups III, IV, and V were three of nine (33%) and seven of nine (78%), 15 of 17 (88%) and 12 of 17 (17%), and three of 20 (15%) and four of 20 (20%), respectively. The treatment with DES alone resulted in the concurrent development of MT and PT in castrated male rats (Group III), and further NBU treatment markedly accelerated the development and growth of MT (Group IV). CB-154 treatment profoundly reduced the incidences of both MT and PT in castrated male rats given DES and NBU (Group V). This treatment also depressed the increase in the number of MT per rat with MT, the pituitary and epididymis weights, and the serum prolactin levels caused by DES treatment. These results indicate that prolonged treatment with CB-154 was effective in the suppression of the concurrent tumorigenesis of mammary and pituitary glands, and the elevation of circulating prolactin levels, by counteracting the continuous stimulatory action of DES. In addition, CB-154 was able to reverse DES-enhanced growth of the epididymis in castrated male rats, suggesting a direct action of prolactin.

Animals↗

In vitro studies of the mechanism of leukemogenesis. II. Characterization of endogenous murine leukemia viruses isolated from AKR thymic epithelial reticulum cell lines.

Thymic epithelial reticulum (TER) cell lines were established from thymuses of a young healthy AKR mouse (A2T), a preleukemic AKR mouse (A6T), and two lymphoma-bearing AKR/Ms mice (ASLT-1 and ASLT-2). Numerous type-C virus particles with occasional budding forms were observed in all cell lines. Expression of XC-detectable, N-tropic, ecotropic virus was observed in every cell line, whereas the presence of xenotropic and mink cell focus-inducing (MCF) viruses could be detected only in TER cells derived from preleukemic and leukemic mice. Expression of xenotropic virus in various cells of newborn and young AKR mice could readily be induced by IUdR treatment, whereas MCF virus was never detected in these cells, with the exception of the A2T cell line after more than 20 passages, in which MCF virus with dual-tropic infectivity emerged in addition to ecotropic and xenotropic viruses. These spontaneous and induced MCF viruses were purified, and their virological properties were characterized. The cloned MCF viruses (MCFs AT1, AT2, AT3, and AT4-IU) showed dual tropism and produced cytopathic effect-like foci in mink lung cells. Preinfection with either ecotropic or xenotropic virus interfered with the infectivity of MCF viruses. Spontaneous leukemogenesis in AKR mice was accelerated by the inoculation of MCF viruses. These findings indicate that TER cells could serve as the host cells for the genetic recombination of the endogenous MuLV; the recombinant MuLV, MCF virus, appears to be most closely associated with leukemogenesis in AKR mice.

AKR murine leukemia virus↗

Establishment and immunologic characterization of 3-methylcholanthrene-induced sarcoma cell lines metastasizing widely in mice and exhibiting distinct and selective propensities for the mode of metastasis.

Successive transplantations of metastatic secondary tumors of a 3-methylcholanthrene-induced sarcoma in (C57BL/Ka X C3H/He)F1 male and female syngeneic mice resulted in the establishment of two unique tumor cell lines with enhanced metastatic potential. Moreover, each line showed distinct and selective propensities for the mode of metastasis. The 1101Pn tumor line, obtained by successive transplantations of metastatic pulmonary nodules, metastasized to many visceral organs via the bloodstream. Another tumor line, 1101Ln, selected by repeated transplantations of lymph node metastases, metastasized to almost all lymph nodes and to the lungs. When the metastatic pulmonary tumor of mice bearing 1101Ln was subcutaneously implanted on the backs of syngeneic mice, the tumor grew locally and eventually metastasized via the lymphatics, with systemic involvement of the lymph nodes. This finding is an indication that the intrinsic properties of tumor cells that form pulmonary metastases in 1101Ln tumor-bearing mice are distinct from those in 1101Pn tumor-bearing mice in terms of metastatic mode. The 1101Pn and 1101Ln tumor lines were nonimmunogenic or less immunogenic than the 505 tumor (the parental, nonselected tumor line). The growth and metastatic action of 505 tumors were enhanced by 400 R whole-body X-radiation, but no such effect was seen with 1101Pn tumors. Pretreatment of mice with OK-432, an immunopotentiator, retarded the growth and metastasis of 505 tumors but exerted little or no effect on 1101Pn tumors. The experimental results suggest that a tumor is composed of a heterogeneous cell population with respect to metastatic potential, metastatic mode, and tumor immunogenicity and that some intrinsic properties of the tumor cell have a primary role in the determination of the mode of cancer metastasis.

Animals↗

Continuous lines of basophil/mast cells derived from normal mouse bone marrow.

Nonadherent tissue culture cell lines were established from normal bone marrow of a variety of mouse strains. The lines possessed morphological and histochemical markers of the basophil/mast cell and contained committed stem cells for metachromatic cells. Their derivation from normal marrow and their lack of tumorigenicity despite long-term culture makes these cell lines potentially important for studies of the mechanisms of allergic reactions and inflammation as well as the differentiation pathways involving this subset of hematopoietic cells.

Animals↗

Leukemogenicity and cell transformation mechanisms in vitro by Gross murine leukemia virus: analysis of virus subpopulations.

The leukemogenic activity of Gross murine leukemia virus adapted to rats was tested in W/Fu rats and NIH/Swiss mice. All animals infected with this virus developed thymic and nonthymic T-cell leukemia with a short latency period. It was observed that cell-free extracts from thymic lymphoma tissue of mice and rats, induced by either Gross murine leukemia virus or Gross murine leukemia virus adapted to rats, consisted of both small-plaque-forming and large-plaque-forming viruses, as determined by the XC plaque test. MCF-type virus was found in these virus complexes. Transformed cell foci were induced in SC-1 cell layers by double infection of the cloned MCF-type virus and an ecotropic virus. SC-1 cells containing transformed cell foci were shown to be tumorigenic upon inoculation into nude mice. The formation of transformed cell foci in mink lung cells was also observed after double infection with the cloned MCF-type virus and a xenotropic virus. The possible mechanism of leukemogenesis by endogenous viruses is discussed.

AKR murine leukemia virus↗

Immunological reaction between sera from neutron-irradiated W/FU rats and mouse mammary tumor virus.

Sera from W/Fu rats from the presence of anti mouse mammary tumor virus (MMTV) antibodies were examined by the use of an immunofluorescence (IF) test and an immune adherence hemagglutination (IAHA) test. Sera from W/Fu rats subjected to neutron irradiation or neutron irradiation followed by grafting of pituitary tumor (MtT) as a source of prolactin gave a positive IF reaction with mouse mammary tumor cells (MMT) producing type-A and type-B virus particles. Nine out of 20 (45.0%) sera from rats given irradiation alone, 17 out of 25 (68.0%) sera from rats subjected to irradiation followed by grafting of MtT and 8 out of 10 (80%) sera from rats given only grafting of MtT gave a positive reaction with the cells, whereas 5 out of 19 (26.3%) sera from normal rats showed a positive reaction with the cells. The specificity of the reaction was confirmed by the distribution pattern of specific fluorescence in MMT cells and by absorption experiments with suitable materials. The results of the IAHA test also showed that some sera from W/Fu rats reacted specifically with purified MMTV, although the incidence of appearance of antibodies in rat sera as detected by IAhA test was low as compared with that detected by IF tests. The IAHA titers of positive rat sera ranged from 1:8 to 1:128. Furthermore, the above results suggest that MtT grafting into W/Fu rats, whether or not they are subjected to neutron irradiation, results in an increase in the frequency of rats carrying antibodies against MMTV.

Animals↗

Mammary carcinogenic effect of low-dose fission radiation in Wistar/Furth rats and its dependency on prolactin.

The mammary carcinogenic effect in rats of low-dose fission radiation and its dependency on prolactin were studied. A total of 141 female W/Fu rats were exposed to 4.8, 8.9, or 19.5 rads of fission radiation that had both fision neutrons of 2.0 million electron volts (MeV) and gamma ray components similar to those produced by the Hiroshima bomb. Only 1 of 48 rats (2.0%) developed mammary tumor (MT) after irradiation alone, whereas 20 of 48 rats (41.6%) developed MT's if prolactin was supplied shortly after irradiation by means of grafting of the prolactin-secreting pituitary tumor. Furthermore, MT's occurred in 11 of 45 rats (24.4%) treated with prolactin as late as 12 months after irradiation, which suggested the long-term survival of radiation-induced dormant MT cells. A correlation was found between the development of MT and the elevation of serum prolactin level; most MT's appeared shortly after the grafted mammotropic pituitary tumor became palpable. The growth of MT's appeared to be promoted by prolactin in collaboration with ovarian hormones; the growth of adenocarcinomas was dependent on prolactin and ovarian hormones, whereas the growth of fibroadenomas appeared to be less hormone-dependent. Much higher biologic effectiveness, especially in the low-dose range, was found with 2.0-MeV fission neutrons compared with 14.1-MeV fast neutrons or 180-kilovolt peak X-rays in rat mammary carcinogenesis.

Adenocarcinoma↗

Synergism of diethylstilbestrol and other carcinogens in concurrent development of hepatic, mammary, and pituitary tumors in castrated male rats.

Castrated male WF rats, given implants of pellets containing 5.0 mg diethylstilbestrol (DES), were given N-butyl-N-nitrosourea (NBU) in small amounts, which alone produced no mammary tumors in intact female rats. Treatment resulted in the high yield of hepatic tumors (HT), mammary tumors (MT), and pituitary tumors (PT) concurrently in each rat. If animals were further treated with prolactin, the development of HT and MT was accelerated, whereas that of PT was suppressed. None of the intact or castrated rats receiving NBU and/or prolactin developed tumors in any tissues if DES treatment was omitted. Exposure of male rats, preconditioned similarly to NBU treatment, to 200 rads of 14.1-MeV fast-neutron radiation also elicited HT, MT, and PT with an efficiency comparable to that of NBU-treated rats. These findings indicate that DES played an essential role in the whole carcinogenic process in each tissue and that castrated male rats, if conditioned properly with estrogens, are useful for the study of the carcinogenesis mechanism in these tissues.

Animals↗

Ultrastructural changes of the dog myocardium in extracorporeal circulation.

The effects of the cardiopulmonary bypass circulation on the cardiac muscle cells were studied electron microscopically. Subendocardial hemorrhage was commonly recognized in both ventricles. However, it appeared earlier and more severely in the right ventricle than in the left ventricle. Clear flocculent areas containing numerous filamentous structures were originated from degradation of myofibrils. Degradation of myofibrils occurred within 1 hour after bypass circulation. Degenerative changes of myocardial cells such as zonal lesions, contraction bands and swelling or condensation of mitochondria appeared in both ventricles. Damages of myocardial cells in right ventricular wall were more severer as compared with those in the left throughout the period of observation.

Animals↗

Chronic toxicity of 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide (AF-2) in mice, with special reference to carcinogenicity in the forestomach.

Chronic toxicity of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2), which had been widely used in Japan as a food additive, was studied in both sexes of ICR/JCL mice by feeding a diet containing AF-2 in a concentration of 0.4% or 0.08%. The experiments confirmed its definite carcinogenicity in the forestomach, with dose dependency; more than 70% of mice fed the higher dose developed tumors, the majority of which were squamous cell carcinomas with metastatic growths, whereas, with a lower dose, fewer tumors occurred, following a longer latent period. In addition, possible leukemogenicity was suggested by a higher incidence in AF-2-fed females (10.8%) over that in control females (3.2%). The development of non-neoplastic lesions in the liver and kidneys, and of amyloidosis in various organs was also observed in some of AF-2-fed mice.

Animals↗