The purpose of these studies was to determine whether the high macrophage content (>50 per cent) of the90Sr-induced osteogenic sarcoma J (Os-J) of recent origin correlated with its immunogenicity or low metastatic potential. Cloning experiments demonstrated that the Os-J tumor is heterogeneous with regard to the production of experimental pulmonary metastases. Immunization-challenge studies in syngeneic mice and comparisons of tumor growth in normal or nude mice established that the slow growing Os-J tumor is poorly immunogenic.In vitro studies demonstrated that the Os-J tumor is highly susceptible to macrophages-mediated lysis. This may explain the slow growth of the tumor in normal recipients with an intact mononuclear phagocyte system, as compared with the more rapid emergence of tumors in macrophage-suppressed mice. However, spontaneous metastases of the Os-J tumor were not observed either in normal or macrophage-suppressed mice. Although a high macrophage infiltration of neoplasms could slow tumor growth, this was not associated with the immunogenicity of the neoplasm and did not appear to limit the spontaneous metastasis of this essentially benign neoplasm.

Determination of the statistical validity of synergism between two carcinogens is conceptually complex. If the dose-response curves of two carcinogens are linear, then the two carcinogens would be in synergism if the tumor yield, when they are administered together, exceeded that obtained by the summation of the tumor yields from the separate testing of the two carcinogens at their respective single doses. For synergism to be established, the difference must be statistically significant.

We present a method for determining the presence or absence of synergism between two carcinogens A and B from the latent period of tumors. The method is applied to data consisting of the means and standard deviations of the times at which tumors become palpable and at which death from tumor occurs in animals of three groups: those given carcinogen A alone, those given B alone, and those given both A and B. Synergism was absent in the data examined.

Susceptibility to cancer implies being easily affected by carcinogen, as well as having an overt spontaneous incidence of cancer. The susceptibility of a population to the development of fatal cancer of a given organ can be represented by a frequency distribution. This distribution depends both upon the genetic susceptibility of the population and upon all environmental carcinogens that have impinged on that population. The method for construction of such a susceptibility distribution has been simplified and applied to experimental data on bone tumor induction with 90Sr in mice, and to bone tumor mortality and prostate cancer mortality in man. The relative susceptibilities of different human organs to the development of fatal tumors can be defined in terms of the spontaneous tumor mortalities.

The thesis was tested that immunization against a murine osteosarcoma virus can reduce the incidence of bone tumors induced by 90Sr. C57BL/6J female mice (190) were divided into three sets of 2 groups. Each set consisted of a control group and an experimental group treated ip with 1.0 muCi 90Sr at 66 days of age. The three sets of groups received the following additional treatments: none (controls), 6 injections of Formalin-inactivated FBJ osteosarcoma virus (vaccinated group), or 6 injections of active FBJ virus (active virus controls). Only 1 bone tumor developed in a mouse not treated with 90Sr in the active virus controls. In 90Sr-treated mice, vaccination reduced bone tumor deaths during the first 600 days from 9 of 36 in controls to 1 of 33 in vaccinated mice (P less than .01), but bone tumor deaths during the entire life-span, 10 of 36 and 5 of 33, respectively, were not significantly different (P = .07). Thus the vaccination procedure delayed the development of bone tumors. In contrast, injection of active virus into 90Sr-treated mice increased the lifetime incidence of bone tumors from 10 of 36 in controls to 19 of 32 (P = .01).

421 C57BL/6J female mice were subdivided into 11 groups. Five of these groups were given 300 rad total body irradiation from a 137Cs source at an age of 65 days. One day later, these irradiated mice were treated intraperitoneally with varying amounts of 90Sr (0, 0.032, 0.10, 0.32, and 1.0 mu Ci/g of body weight). Five groups of mice that had not been irradiated were treated on the same day with the same doses of 90Sr as given the five irradiated groups, and a sixth unirradiated group was treated with 2 mu Ci/g body weight. Each mouse treated with 90Sr and still alive was monitored between 249 and 303 days later in a total body well scintillation detector; mice with counts that differed by more than approximately 50% from the mean for their group were eliminated. A total of 402 mice were accepted for the experiment; these mice were followed to the end of their life span and then autopsied. Mice treated with the highest doses of 90Sr (1.0 and 2.0 mu Ci/g) experienced significantly elevated number of deaths from infections relative to the control group; these deaths occurred relatively early after 90Sr injection, and were particularly severe in the group of mice that had received 300 rad of external irradiation in addition to 1.0 mu Ci90Sr/g. There was no evidence of synergism between 90Sr injection and 300 rad external irradiation for production of bone tumors. Tumors of the type that occur spontaneously in C57BL/6J mice appeared to be more frequent in 90Sr-treated mice and in externally irradiated mice than in controls, but the numbers of excess tumors in these groups were not statistically significant (P less than 0.09).

The aim of this study was to investigate the compound 4‐nitro‐1‐cyclohexyl‐3‐ethoxy‐2‐oxo‐3‐pyrroline (NOPYE) and some related compounds for skin sensitization in guinea pigs, as the first step in a search for more effective skin sensitizers for immunotherapy of cutaneous tumors. In guinea pigs, NOPYE and NOPYE‐L‐alanine produce far milder delayed hypersensitivity reactions than DNCB. Both NOPYE and DNCB fail to act as adjuvants for skin sensitization to tuberculin purified protein derivative (PPD) and ovalbumin (OV). This suggests an explanation for the lack of effectiveness of DNCB in immunotherapy of metastases: DNCB may be relatively ineffective as an adjuvant for production of specific antitumor immunity. Such adjuvant activity may be essential if the action of the immunotherapeutic reagent is not to be confined to its site of application but is to be effective at the site of distant metastases.

Faculty in 80 to 90 per cent of private colleges and universities, and in 40 per cent of public institutions, are eligible to participate in the Teachers Insurance and Annuity-College Retirement Equities Fund (TIAACREF) retirement program.1 To many contributors, the accumulation of funds in this program represents the main source of income during retirement. The choice of how to apportion one's contributions between TIAA and CREF is therefore a vital one.2 During my sixteen years of participation, I have not seen a simple, straightforward comparison of the longterm earning performances of TIAA and CREF. Certainly, the annual reports from TIAA-CREF have been helpful towards that goal. Nevertheless, neither I nor my colleagues have been able to make a direct comparison of the performances of TIAA and CREF from these reports. In order to make such a comparison, I present Table 1 based on data furnished to me by TIAA-CREF. This table has been checked for accuracy by TIAA-CREF.8 1 hope it will be very helpful to professionals who are as simple-minded in financial matters as I am. While it is true that the past may not be indicative of future performance, knowledge of the certain past seems vital for extrapolations into the uncertain future. The headings in Table 1 give the year in which monthly investments in TIAA and CREF were begun, starting on January 1. Column 1 gives the year at the end of which the net accumulated funds in TIAA and in CREF are compared. The basis for the comparison is that identical amounts have been paid into these two funds. Also, it is assumed that payments into the funds increase by 6 per cent each year, a reasonable estimate for the rate at which salaries increase from year to year. The body of the table gives the ratios of the funds accumulated in TIAA and in CREF. This ratio represents a direct comparison of the performance of the two

Several immunization regimens for preparation of ALK-NABS were compared. One series of eight intravenous injections spaced over 5 weeks gave an ALK-NABS with potency and specificity that could be bettered only slightly by a second series of four injections spaced over 2 weeks, whereas a third series of injections was deleterious. Use of late immune antisplenocyte NABS for such immunizations produced ALK-NABS reagents with the highest in vitro specificity to leukemia cells relative to splenocytes after absorption, whereas early immune antisplenocyte NABS gave ALK-NABS with the highest antileukemia specificity relative to thymocytes. Therapy experiments with leukemias L1210 and BW-A showed increased survival times for isogeneic mice injected intraperitoneally with 10(3) (L1210 only), 10(4), and 10(5) (higher significance for L1210) cells, when ALK-NABS was given intraperitoneally in high dose on 4 or 5 successive days starting 1 day after inoculation of leukemia cells. In additional experiments with 10(5) cells given intraperitoneally, lower doses of ALK-NABS were progressively more effective with L1210 leukemia, producing some survivors without any apparent toxicity from the antiserum. In contrast, a similar experiment with leukemia BW-A was entirely negative. Addition of guinea pig serum to already excessive amounts of antiserum was not helpful.