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[CANCER RESEARCH 33, 1598 1603, July 1973] Specific Antigenicity of Tumors and Immunological Tolerance in the Rat Induced by Friend, Gross, and Rauscher Viruses1 H. Kobayashi, N. Kuzumaki, E. Gotohda, IM. Takeichi, F. Sendo, M. Hosokawa, and T. Kodama Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan SUMMARY Several lines of rat tumors grew only in Friend, Gross, and Rauscher virus-tolerant rats that had received injec tions of each of these viruses at birth. When the tumors were transplanted into the virus-tolerant rats that had received injections of the other types of murine leukemia virus, they grew initially, and then regressed. Tumors did not grow in normal rats. The same is true in the methylcholanthrene-induced tumors that had been given injections of murine leukemia viruses. It was deduced from these re sults that the transplantation antigen of tumor cells that were induced by infection with Friend, Gross, and Rauscher viruses may contain an antigen common to all three vi ruses and also an antigen that is individually specific, and that the host's immunological tolerance (induced by the neonatal injection of either Friend, Gross, or Rauscher virus) may consist of the tolerance common to all three viruses and, also, of the tolerance that is individually spe cific. INTRODUCTION Much remains to be studied about the relationship of the transplantation antigens that are induced by Friend, Gross, Rauscher, and other MLV. We previously reported that Friend virus-induced tumors that developed in rats given injections of Friend virus at birth grew only in the Friend virus-conditioned and -tolerant rats, and that they did not grow in syngeneic normal adult rats (6). In this study we attempted to determine whether the same result can be extensively observed in the tumors induced by Gross and Rauscher viruses. We also attempted to reveal the re lationship of the transplantation antigen to the tumors in duced by Friend, Gross, and Rauscher viruses that devel oped after the tumors were transplanted into virus-tolerant rats that had received injections of MLV at birth. MATERIALS AND METHODS Friend Virus. Ten years have passed in our laboratory 'This work was supported in part by a research grant for cancer re search from the Ministry of Education of Japan. 2The abbreviations used are: MLV, murine leukemia virus: WKA/Mk. Wistar-King-Aptekman. Received July 25, 1972; accepted March 19, 1973. 1598 since the initiation of serial passages of the Friend virus. The virus was recovered [by a modification of the method of Chenaille et al. (1)] from the enlarged spleen of Friend leukemia dd/Om mice. Gross Virus. A rat-adapted strain of Gross virus was used. The Gross virus was kindly supplied by Dr. K. Yokoro, Hiroshima University, Hiroshima, Japan. It was previously sent by Dr. H. Okano, Kyushu University, Fukuoka, Japan, who initially received the virus from Dr. J. Furth, Columbia University, New York, N. Y. The Gross virus was recovered from the enlarged thymus of WKA/Mk rats given injections of Gross virus at birth by the same method used with the Friend virus. Rauscher Virus. Rauscher virus was sent by Dr. K. Yokoro, Hiroshima University, Hiroshima, Japan. Re covery of this virus was similar to that of Friend virus. Normal Rats. Inbred WKA/Mk rats were used. They were bred in the Experimental Animal Center by Dr. S. Makino and Dr. M. Sasaki, Faculty of Science, Hokkaido University, Sapporo, Japan. Skin transplantation suc ceeded in all cases. Tolerant Rats. Adult WKA/Mk rats that had been given i.p. and s.c. injections of undiluted murine leukemia virus within 48 hr after birth were used as tolerant rats. Friend and Rauscher virus-tolerant (2- to 3-monthold adult) rats received neonatal injections of Friend and Rauscher virus, and the treatment for both groups was the same. Gross virus-tolerant rats were only 1 to 2 months old and received injections of Gross virus at birth. Tumors. WFT tumors were established from the en larged spleen of WKA/Mk rats approximately 200 days after the neonatal injection of Friend virus and were maintained in Friend virus-tolerant rats. WGT tumors were established from the thymus of WKA/Mk rats 2 to 3 months after the neonatal injection of Gross virus; these were maintained in Gross virus-tolerant rats. WRT tumors were established from the spleen of WKA/Mk rats ap proximately 200 days after the neonatal injection of Rauscher virus and were maintained in Rauscher virustolerant rats. Morphological studies of the WFT, WGT, and WRT tumors have already been described (10). Thir teen lines of WFT, 10 lines of WGT, and 3 lines of WRT tumors are now available in both the solid and ascites forms. The tumors used for the experiments had been transplanted for less than 15 generations, except for the WFT-3 tumor, which was transplanted for less than 35 generations. As the control tumor, Sato lung cancer in duced by 4-nitroquinoline-/V-oxide in Donryu rats, was CANCER RESEARCH VOL. 33 Downloaded from cancerres.aacrjournals.org on June 16, 2017. © 1973 American Association for Cancer Research. Friend, Gross, and Rauscher Tumors in Rats sent by Dr. S. Oboshi, National Cancer Center, Tokyo, gressed. A total of 424 of the 434 Friend virus-tolerant Japan, and FMT-15, induced by methylcholanthrene in rats (97.7%) died of tumor growth; only 3 of the 168 Fischer rats, was sent by Dr. M. Aizawa, Department of normal rats (1.8%) died of tumor growth, and the re Pathology, Hokkaido University School of Medicine, mainder survived more than 3 months without tumor de Sapporo, Japan. The LFT-2 tumor was induced by Friend velopment. Lethal Growth of Gross Virus-induced Tumors (WGT). virus in Long-Evans rats. The LFT-2 tumor was maintained in Friend virus-tolerant Long-Evans rats. All tumors were When 10 lines of Gross virus-induced primary tumors (WGT), all successfully established as transplantable usually maintained in the ascites form. Artificial Infection with MLV. Methylcholanthrene- lines, were transplanted i.p. into Gross virus-tolerant induced ascites tumor KMT-17 of the WKA/Mk rat was rats, all lines thrived and, in nearly all cases, killed the artificially infected with MLV's. For the virus infection, host. In contrast, the WGT line did not grow well in the KMT-17 tumor was transplanted i.p. into tolerant normal rats and, in all cases (even if they grew initially), rats that had received injections of Friend, Gross, or the tumors later regressed. With all 10 lines of WGT, 98 Rauscher virus after the tumor was mixed with the virus of the 101 Gross virus-tolerant rats (97%) died of tumor at transplantation. After transplantation of the tumor for growth, but none of the 50 normal rats died of tumor 1 to 2 generations, the success of the artificial infection growth (Table 2). General results of the transplantation of WGT appear quite similar to the results of WFT trans of the virus and the subsequent appearance of a new anti plantation. gen on the cell surface were proved by electron micro Lethal Growth of Rauscher Virus-induced Tumors scopy, cytotoxicity test, and immunofiuorescence (8, (WRT). When 3 lines of Rauscher virus-induced tumors 14, 16). were transplanted into Rauscher virus-tolerant rats, the tumors thrived and killed the host in all 59 cases. In RESULTS contrast, none of the 48 normal rats were killed (Table 3). It was therefore concluded that all lines of tumors induced Lethal Growth of Friend Virus-induced Tumors (WFT). in rats by Friend, Gross, and Rauscher viruses thrive Thirteen lines of Friend virus-induced tumors (each con only in virus-tolerant rats given injections of the cor sisting of 10' to 10" cells) were transplanted i.p. into responding virus at birth, and that they do not grow or Friend virus-tolerant and normal WKA/Mk rats (Table 1). thrive in normal rats. All WFT lines grew well, and they killed the Friend virusGrowth Pattern of Each MI. V-induced Tumor. Two tolerant rats; however, in normal rats they either did not lines of WFT and 3 lines each of WGT and WRT were grow at all or, even if they grew initially, they later re- transplanted into each type of tolerant rat. As shown in Table 4, both WFT-3 and WFT-13 tumors thrived and killed all of the Friend virus-tolerant rats, but they did Tablel not thrive in the Gross and Rauscher virus-tolerant rats, Lethal growth of Friend virus-induced tumors inoculated i.p. in Friend except for some lethal tumors in the Rauscher virusvirus-tolerant and normal WKA/Mk rats tolerant rats. rats"WFT-1WFT-2WFT-3WFT-4WFT-5WFT-6WFT-7WFT-8WFT-9WFTFriend virus-tolerant )lLeinai -i !. Table 2 innormal growths Lethal growth of Gross virus-induced tumors inoculated i.p. in Gross rats/no. virus-tolerant and normal WKA/Mk rats tested3/380/53"0/260/90/40/30/50/40/263/168(1.8%) tested128/129113/11384/8425/259/129/97/1311/1113/132/22/22/219/19424/434(97.7%)Meansurvival(days)33.210.219.520.052. rats"WGT-1WGT-2WGT-3WGT-4WGT-5WGT-6WGT-7WGT-8WGT-9WGTGross virus-tolerant atk.tlLethal y21.825.435.024.3e36.0e28.5e21.0e18.21 innormal growths rats/no. tested8/924/2515/1531/314/44/52/22/24/44/498/101(97%)Me tested0/20/150/140/130/2 10WFT11WFT12WFT13TotalLethalgrowths/no. 10Total,Lethalgrowths/no. " Given injections of Friend virus at birth. " Regression of the tumor is observed after the initial growth. WFT-2N, obtained as a variant of WFT-2, grew lethally in all of the 141 normal rats (9). e Inoculated s.c. JULY 1Given injections of Gross virus at birth. 6 Inoculated s.c 1973 Downloaded from cancerres.aacrjournals.org on June 16, 2017. © 1973 American Association for Cancer Research. 1599 Kobayashi et al. leukemia virus that induced the tolerance were then trans planted. For example, after the immunization of Gross virus-tolerant rats with WFT-13 and WRT-2 tumors, the WGT-4 tumor was transplanted. As a control, WGT-4 was rats"Lethalgrowths/no. virus-tolerant transplanted into unimmunized Gross virus-tolerant rats, and these were compared with each other (Table 5). No innormal signs of a breakdown of immunological tolerance were ob rats/no. tested34/3414/1411/1159/59(100%)Meansurvival(days)18.818.222.8Lethalgrowths tested0/40/240/200/48(0%) served, from the viewpoint of survival days or transplantability, or from the growth curve of the tumor. This may WRT-1WRT-2WRT-3TotalRauscher indicate the specificity and comparative stability of the im munological tolerances induced by MLV in rats. Lethal Growth of Methylcholanthrene-induced KMT17 Tumor Artificially Infected with MLV's. For repro duction of the experimental results obtained above, a 'Given injections of Rauscher virus at birth. methylcholanthrene-induced KMT-17 tumor that de veloped apart from the MLV in the WKA/M k rat was artificially infected with Friend, Gross, and Rauscher vi WGT-2, WGT-3 and WGT-4 tumors thrived and killed ruses. The virus-infected tumor was then transplanted the Gross virus-tolerant rats, whereas they did not thrive or into each strain of virus-tolerant rats or into normal rats. kill either Friend or Rauscher virus-tolerant rats, even Friend virus-infected KMT-17 (FV-KMT-17) grew after considerable growth of the local tumors was ob and killed only Friend virus-tolerant rats, and Gross virus-infected KMT-17 (GV-KMT-17) grew and killed served. There were similar findings with the WRT tumors. only Gross virus-tolerant rats. FV-KMT-17 did not kill WRT-1, WRT-2, and WRT-3 thrived and killed Rauscher Gross or Rauscher virus-tolerant rats, in which the tumor virus-tolerant rats but did not grow or kill the Gross grew initially and later regressed. GV-KMT-17 did not virus-tolerant rats. However, when the WRT tumors kill Friend or Rauscher virus-tolerant rats, in which the were inoculated into Friend virus-tolerant rats, the tumor grew initially and later regressed. However, WRT-1 and WRT-3 tumors (in particular) killed the host, Rauscher virus-infected KMT-17 (RV-KMT-17) grew and with tumor development at the site of transplantation, but killed Rauscher virus-tolerant rats and also some of the when WRT-2 was inoculated s.c. into Friend virus-tolerant Friend virus-tolerant rats (Table 6). These findings indicate rats, the tumor regressed after the initial growth (40 x 40 that leukemia virus-infected tumors thrived in tolerant mm) at the inoculation site. However, in 11 of 14 cases, the tumor metastasized and appeared again in the lymph Table 4 nodes and organs in the abdominal cavity nearly 2 Lethal growth of each murine leukemia virus-induced tumor inoculated months after the 1st inoculation. s.c. in tolerant WKA/Mk rats given injections (at birth) of each murine The average pattern of the growth curves of WFT-13, leukemia virus WGT-2, and WRT-2 tumors in each virus-tolerant rat is Lethal growths in tolerant rats/ shown in Chart 1. Although all tumors regressed after no. tested temporary growth, the maximum size of the tumors differed with each tumor type and in each type of rat. For example, while the WGT-2 grew in Rauscher virus- TumorFriend virus84/84" virus0/3 virus2/50/6 tolerant rats to a maximum size of only 20 x 20 mm, it virus-induced grew to a maximum size of 30 x 30 mm in Friend virusWFT-3 tolerant rats. Similarly, the WRT-2 grew to a maximum 19/19°Gross 0/11Rauscher WFT-13Friend size of approximately 20 x 20 mm in Gross virus-tolerant rats. However, in Friend virus-tolerant rats, it grew to a 103/103 0/14 2/11 Total maximum size of more than 40 x 40 mm and regressed; virus-induced occasionally it killed the host by metastasis. In short, Gross 24/25" WGT-2 0/12 0/2 Friend virus-tolerant rats were more tolerant to the growth 15/15" WGT-3 0/8 0/2 of these tumors than either Gross or Rauscher virus-tol 31/31° WGT-4 0/6 0/2 erant rats, and normal rats are least tolerant to all 3 (WFT, 70/71 0/26 0/6 Total WGT, and WRT) types. Specificity of Immunological Tolerance of Rats Given Rauscher virus-induced 34/34" Neonatal Injections of MLV. Attempts were made to WRT-1 9/10 0/3 14/14" WRT-2 determine whether the immunological tolerance induced 11/14 0/1 11/11" by the MLV's could be broken down after the regression WRT-3 0/4 9/10 of the tumors induced by the other types of MLV. Re 29/34 59/59 Total 0/8 peated immunizations with live tumor cells of the different 'The same results were presented in Tables 1, 2, and 3. types were performed s.c. and tumors induced by the same Table 3 Lethal growth of Rauscher virus-induced tumors inoculated i.p. in Rauscher virus-tolerant and normal WKA /Mk rats 1600 CANCER RESEARCH VOL. 33 Downloaded from cancerres.aacrjournals.org on June 16, 2017. © 1973 American Association for Cancer Research. Friend, Gross, and Rauscher Tumors in Rats Friend Rauscher Gross tolerant tolerant tolerant Normal l' u WFT-13 5 30 CO K 20 H IQ 40 WGT-2 10 40 30 WRT-2 20 10 weeks 1234 weeks after inoculation Chart I. Growth curve of various MLV-induced tumors inoculated s.c. in tolerant WKA/Mk rats given injections (at birth) of other MLV's (a, metastatic growth of the WRT-2 killed the Friend virus-tolerant rat later). weeks weeks Table 5 Speciflcily of immunological tolerance of WKA/Mk rats given injections of MLV at birth MLV-induced tumors were transplanted in correspondingly tolerant rats that had been immunized with live tumors induced by other types of MLV. growths in tolerant testedImmunized3/3 rats/no, withGross Rat virus-tolerant WRT-3Friend virus-tolerant WRT-2Rauscher virus-tolerant Immunized immunized2/2 withWGT-4 WFT-13, WRT-2 WFT-13, (20.0)" WGT-4WFT-13 2/2(13.0)4/4(30.0) WGT-2, WGT-2 WGT-3 WGT-4. WGT-4 LFT-2 WGT-3, WFT-13 WFT-13 WFT-13 WFT-13WRT-2 4/4 (30.7) 5/5(28.5) I/I (41.0) I/I (35.0)1/2 WFT-13, WGT-3. 4 WGT-2, WGT-4, WFT-13 WGT-4LFT-2 WRT-2 WRT-2WRT-3 (30.0) 3/3 (22.0) I/I (25.0)1/1 WGT-3, WFT-13 WGT-4, WFT-13Challenged" WRT-3 WRT-3Lethal (27.0)I/I (27.0) 2/2 (26.0)Not (20.0)28/28 (31.5)3/3(25.3)4/4(40.5) " Challenged s.c. 1 to 3 weeks after the final immunization. *Numbers in parentheses, mean survival (days). JULY 1973 Downloaded from cancerres.aacrjournals.org on June 16, 2017. © 1973 American Association for Cancer Research. 1601 Kobayashi et al. Table 6 Lethal growth of methylcholanthrene-induced KMT-17 tumor cells (IO6) artificially infected with Friend, Gross, and Kauscher virus in tolerant WKA /Mk rats developed or chemically induced tumors became un able to grow in syngeneic normal rats or primary autoch thonous rats after they were artificially infected with the Friend virus, and that the Friend virus-infected tumors grew only in Friend virus-tolerant rats or immunosuppres testedGross in tolerant rats/no, sive rats (5, 8, 15). The above findings are similar in nature and may be termed "xenogenization of tumors," which is growths in virusvirusvirusnormal defined as the immunological regression of tumors without tolerant tolerant tolerant rats/no, the aid of previous immunization in the host. In this report DonorFV-KMT-17"GV-KMT-17"RV-KMT-I7CLethalFriend rats3/30/62/30/4"growths rats0/912/120/2Rauscher rats0/40/24/43/3"Lethal tested0/430/90/6 it was clarified that xenogenization of rat tumors may be produced by infection with Gross and Rauscher viruses as well as with Friend virus. There was no difference be tween each of the murine leukemia virus-induced tumors with regard to their ability to produce xenogenization of " KMT-17 cells artificially infected with Friend virus were inoculated tumors in rats. :. Concerning the transplantation antigens of the tumors 6KMT-17 cells artificially infected with Gross virus were inoculated induced by Friend, Gross, and Rauscher viruses, it is c. ' KMT-17 cell artificially infected with Rauscher virus were inoculated probable that an antigen common to all and (also) an in c. dividually specific antigen may exist in each tumor. It is " A small number of RV-KMT-17 cells (IO4) were inoculated. also probable that a tolerance common to all and an in dividually specific tolerance may exist in tolerant rats. rats induced by the corresponding leukemia virus but This is because both virus-induced tumors and tumors did not thrive in tolerant rats induced by different types of artificially infected with the virus can grow lethally in leukemia virus, there were no lethal effects, with the excep tolerant rats induced by the corresponding virus and not tion of some cases of RV-KMT-17 in Friend virus-tolerant grow in normal adult rats and also because the tumors grow temporarily and eventually regress in tolerant rats induced rats. They did not thrive in normal adult rats. These re by different types of MLV, which result may not be due to sults are similar to those obtained in the previous exper iments with the MLV-induced tumors WFT, WGT, and the nonspecific immunosuppression of the host. Antigenic similarities between Friend and Rauscher WRT. viruses have been noted (12). However, this does not Transplantation of Allogeneic Tumors in Tolerant WKA/ Mk Rats. In order to determine the immunosuppressive mean a complete correspondence of the transplantation effects of MLV's in the tolerant host, we transplanted al- antigen, as was indicated in our experiments. Although the Rauscher virus-induced tumors or the tumors ar logeneic tumors (such as Sato lung cancer in Donryu rats and FMT-15 in Fischer strain rats) s.c. into Friend, tificially infected with Rauscher virus grew and eventually Gross, and Rauscher virus-tolerant WKA/Mk rats, and killed most of the Friend virus-tolerant rats, the growth the growth rates of the tumors in tolerant and normal rats pattern in these rats was evidently different from that in Rauscher virus-tolerant rats. Moreover, the Friend were compared (Table 7). In tolerant rats, both allogeneic tumors showed the same transplantation rate and growth virus-induced tumors or the tumors artificially infected with Friend virus regressed in Rauscher virus-tolerant rats. curves as in normal rats. It was therefore assumed that the growth of MLV-induced tumors in each strain of Therefore, it may be concluded that the transplantation virus-tolerant rats (as shown in the preceding experiments) antigen induced by Friend virus seems to possess the Rauscher-specific transplantation antigen as a part of it, may depend entirely upon the specific immunological tol and that most of the Rauscher virus-specific transplan erance of the host toward the specific transplantation antigen of each tumor and may not depend upon the tation antigen may be involved in the Friend virus-spenonspecific suppression of immunological reactivity of the host. The healthy existence of cellular immunity, as tested Table 7 by allogeneic skin transplantation, delayed-type hypersenLethal growth of allogeneic tumors inoculated s.c. into tolerant and sitivity of 2,5 dinitrochlorobenzene, and graft-versusnormal WKA/Mk rals host reaction, in Friend and Gross virus-tolerant rats is described in a manuscript being prepared (N. Takeichi, Lethal growths in testedAllogeneic tolerant rats/no, N. Kuzumaki, and H. Kobayashi. Immune Responses growths in of the Rat Inoculated with Friend and Gross Viruses at normal Birth, in preparation). virus0/2Lethal rats0/5 virus0/10" tumorsSato DISCUSSION It has been reported that Friend virus-induced tumors grew only in Friend virus-tolerant rats and did not grow in normal adult rats (6). We also reported that spontaneously 1602 lung cancer" FMT-15"Friend 0/2Grossvirus0/10/2Rauscher 0/2 "4-Nitroquinoline /V-oxide-induced lung cancers were transplanted in Donryu rats; 5 x IO5cells were used. * Methylcholanthrene-induced tumors were transplanted in Fischer rats; 1 x IO7cells were used. CANCER RESEARCH VOL. 33 Downloaded from cancerres.aacrjournals.org on June 16, 2017. © 1973 American Association for Cancer Research. Friend, Gross, and Rauscher Tumors in Rats cific transplantation antigen. On the other hand, the Gross REFERENCES virus may be a component of the Friend or Rauscher virus 1. Chenaille, P., Levy, J. P., Tavitian, A., and Biron, M. Routine group, so that the Gross virus-specific transplantation an Method for Concentration and Partial Purification of a Murine tigen may be involved in the Friend or Rauscher virusLeukemia Virus (Rauscher). Nature, 213: 107 109, 1967. specific transplantation antigen (2, 3, 12, 13). Our trans 2. Geering, G., Old, L. J., and Boyse, E. A. Antigens of Leukemias plantation results indicated that the Gross virus-induced Induced by a Naturally Occurring Murine Leukemia Virus: Their transplantation antigen has Gross virus specificity, in Relation to the Antigens of Gross Virus and Other Murine Leu addition to their common antigen, which is different from kemia Viruses. J. Exptl. Med., 124: 753-772, 1966. the Friend or Rauscher transplantation antigen. We have 3. Glynn, J. P., McCoy, J. L., and Fefer, A. Cross-resistance to the attempted to show the general relationship between Transplantation of Syngeneic Friend, Moloney, and Rauscher Friend, Gross, and Rauscher virus-induced transplanta Virus-induced Tumors. Cancer Res., 28: 434 439, 1968. 4. Herberman, R. B. Serological Analysis of Cell Surface Antigens of tion antigens and the tolerance of the host (Chart 2). The Tumors Induced by Murine Leukemia Virus. J. Nati. Cancer Inst., size of the circles indicates the possible strength of the 48: 265 271, 1972. transplantation antigen and also the immunological tol 5. Kobayashi, H. Growth of Rat Tumor Cells Infected with Friend erance of the host. Virus: An Approach to the Immunological Treatment of Cancer. All of the above-described results were obtained by in In: L. Severi (ed.). Immunity and Tolerance in Oncogenesis. IV Pro vivo experiments with rats, and an in vitro serological ex ceedings of the Perugia Quadrennial International Conference on Can periment (11) yielded similar results with more details. cer, pp. 637 659. Perugia. Italy: Division of Cancer Research, Univer Herberman (4) recently described similar results, from sity of Perugia, 1970. serological studies regarding the relationship of Rauscher 6. Kobayashi, H., Hosokawa, M., Takeichi, N., Sendo, F., Kodama, T. and Moloney virus-induced mouse tumors (with the use of Transplantable Friend Virus-induced Tumors in Rats. Cancer Res., rat antiserum) to Gross virus-induced tumors in rats. 29: 1385 1392, 1969. 7. Kobayashi, H., Kodama, T., Sendo, F., Hosokawa, M., and Takeichi, Note that our results were from experiments with rats N. The Role of the Virus in the Growth of Leukemia Cells. Kokenand we were not able to duplicate them in experiments shi, 19: 129-135, 1967. with mice. For example, Friend virus-induced tumors or 8. Kobayashi, H., Sendo, F., Shirai, T., Kaji, H., Kodama, T., and Friend virus-infected tumors in mice are inhibited by Saito, H. Modification in Growth of Transplantable Rat Tumors previous immunization with Friend virus only in the small Exposed to Friend Virus. J. Nail. Cancer Inst., 42: 413 419, 1969. number of cells inoculated and never regress by them 9. Kobayashi, H., Shirai, T., Takeichi, N., Hosokawa, M., Saito, H., selves if not immunized (7). Sendo, F., and Kodama. T. Antigenic Variant (WFT-2N) of a Trans A possible explanation is that the transplantation anti plantable Rat Tumor Induced by Friend Virus. European J. Clin. gen induced by Friend, Gross, and Rauscher viruses is Biol. Res., 15: 426 428, 1970. 10. Kodama, T., Kuzumaki, N., Takeichi, N., and Kobayashi, H. extremely high in antigens when produced in rats and com Morphological Studies of Tumors in Rats Induced by Murine Leu paratively low in antigens when produced in mice. Friend Rauscher Chart 2. Relations of transplantation antigen and immunological tol erance induced by Friend, Gross, and Rauscher viruses in rats. JULY kemia Viruses (Friend, Rauscher and Gross). Trans. Soc. Pathol. Japan, 60: 106-107, 1972. 11. Kuzumaki, N., Takeichi, N., Sendo, F., Kodama, T., and Kobayashi, H. Correlation between Various Cell-surface Antigens Induced by Murine Leukemia Virus in the Rat: Serological Analysis. Intern. J. Cancer, in press. 12. McCoy, J. L., Fefer, A., and Glynn. J. P. Studies on the Neutraliza tion of the Oncogenicity of Friend, Moloney and Rauscher Vi ruses. Cancer Res., 28: 942 946, 1968. 13. Old, L. J., Boyse, W. A., and Stocken, E. The G (Gross) Leukemia Antigen. Cancer Res., 25: 813 819, 1965. 14. Saito, H. Immunofiuorescence Studies on the Transplantable Rat Tumor Cells Infected with Friend Virus. Gann, 61: 253 258, 1971. 15. Sendo, F., Kaji, H., Saito, H., and Kobayashi, H. Antigenic Modifi cation of Rat Tumor Cells Artificially Infected with Friend Virus in the Primary Autochthonous Host. Gann, 61: 223 226, 1970. 16. Shirai, T., Kaji, H., Takeichi, N., Sendo, F., Saito, H., Hoso kawa, M., and Kobayashi, H. Cell Surface Antigens Detectable by Cytotoxic Test on Friend Virus-induced and Friend Virus-infected Tumors in the Rat. J. Nati. Cancer Inst., 46: 449 460, 1971. 1973 Downloaded from cancerres.aacrjournals.org on June 16, 2017. © 1973 American Association for Cancer Research. 1603 Specific Antigenicity of Tumors and Immunological Tolerance in the Rat Induced by Friend, Gross, and Rauscher Viruses H. Kobayashi, N. Kuzumaki, E. Gotohda, et al. Cancer Res 1973;33:1598-1603. Updated version E-mail alerts Reprints and Subscriptions Permissions Access the most recent version of this article at: http://cancerres.aacrjournals.org/content/33/7/1598 Sign up to receive free email-alerts related to this article or journal. To order reprints of this article or to subscribe to the journal, contact the AACR Publications Department at [email protected]. To request permission to re-use all or part of this article, contact the AACR Publications Department at [email protected]. Downloaded from cancerres.aacrjournals.org on June 16, 2017. © 1973 American Association for Cancer Research.