Morphologic aspect of the placenta in young and adult pregnant rats bearing Walker 256 carcinoma

In the present study we investigated the influence of Walker 256 tumor growth on the modification of placental morphology and on fetal development in young and adult pregnant rats. After mating, female rats were divided into six groups: young control pregnant (Y), young pregnant with tumor (Yw), young pregnant injected with ascitic fluid (Ya), adult control pregnant (A), adult pregnant with tumor (Aw), and adult pregnant injected with ascitic fluid (Aa). Rats from tumor-bearing groups (Yw and Aw) were injected with 2.5 x 10(6) viable tumor cells into the right flank. Rats from Ya and Aa groups received daily inoculations of ascitic fluid (2.0 ml, i.p.) obtained from tumor-bearing rats without tumor cells. After 21 days, all animals were killed and the placentas were weighed and fixed with paraformaldehyde for histological analysis. Compared with control groups (Y and A), both tumor-bearing groups (Yw and Aw) presented the following changes: i) hemorrhage in the decidua and in the trophoblast giant cell layer; ii) disarrangement of the spongy zone, iii) restricted delimitation of the maternal and fetal blood vessels in the placental labyrinth; iv) hemorrhage and edema in the placental labyrinth. Similar results were observed in the placenta of groups injected with ascitic fluid (Ya and Aa). These results indicate that tumor development during pregnancy can have deleterious effects on placenta and fetus. These observations extend our previous data of extensive fetal reabsorption in both pregnant tumor-bearing and ascitic fluid-injected animals. These changes in placental morphology may be related to the synthesis and release of some factors by the tumor and the host cells, which could act directly or indirectly on placental tissue.     

Human antibody SC-1 reduces disseminated tumor cells in nude mice with human gastric cancer

Advanced gastric cancer is a systemic disease that requires adjuvant therapy targeted at eliminating disseminated tumor cells (DTCs). We investigated whether the apoptosis-inducing human monoclonal IgM antibody SC-1 was able to reduce the number of disseminated gastric cancer cells in blood and bone marrow. Human gastric tumor specimens with positive expression of the SC-1 receptor were transplanted in nude mice with metastasizing gastric cancer. After tumor growth (4-6 weeks) animals were randomly allocated to intraperitoneal 100 microg SC-1 (n=23) or 100 microg human IgM (n=23). One week later, animals were sacrificed and blood and bone marrow specimens were obtained. A nested RT-PCR for cytokeratin 20 (CK-20) from blood and bone marrow of mice was performed for detection of disseminated tumor cells. Animals receiving SC-1 had significantly fewer DTCs than did control animals (p=0.0011). None of the SC-1 mice had DTCs simultaneously in both blood and bone marrow versus four of the control animals (p=0.0363). The reduction of DTCs in SC-1 animals was due to reduction in bone marrow (p=0.032 compared to controls), but not in blood (p=0.1158). Treatment with SC-1 significantly reduced the number of DTCs in bone marrow in this animal model.     

Calorie restriction: effect on growth of human tumors heterotransplanted in nude mice

The presence of 4 human malignant tumors (1 breast, 1 lung, and 2 colon carcinomas) growing subcutaneously as heterotransplants in nude mice did not significantly affect the body weights of adult animals until the tumors reached very large dimensions (tumor wt greater than 15% of the body wt). However, a colon carcinoma (HT 29) induced a cessation of the natural rate of body weight increase when it grew in young adults (animals weighing approximately equal to 25 g which will gain 6 g or approximately equal to 25% body wt in 1 mo). Calorie restriction at all the levels tested (8, 6, 4, and 2 g/day/mouse) with standard pelletized mouse food produced both weight loss in the animals (with and without tumor) and a lowering of the growth rate of all the 4 tumors tested growing at a subcutaneous site and/or under the kidney capsule. Each tumor responded differently to the calorie restriction. The 4 tumors tested grew equally in both male and female nude mice. Young animals weighing 20 g inoculated with a fifth tumor (MeWo melanoma) exhibited tumor growth inhibition proportional to restriction of calorie intake. Their survival, however, did not improve.     

DNA alkylation by nitrosobis-(2-oxopropyl)amine in rats of different ages

We have examined the methylation of liver DNA (O6- and N7-methylguanine) by nitrosobis-(2-oxopropyl)amine (BOP) in male and female rats at various ages, following treatment with 2.5 mg of BOP; this dose given twice weekly for 30 weeks induces tumors in all animals. Except in young rats there was more methylation in female rat liver than in male rat liver, when adjusted for different sizes of the animals. There were differences in the extent of methylation between young (4 weeks) and older rats, but not between young adult (20 weeks) and old adult (65 weeks) males; the latter developed liver tumors when treated with BOP, and the former did not. There was no obvious relation between increased susceptibility to liver tumor induction by BOP and the extent of alkylation of liver DNA. Methylation of DNA was lower in the kidney than in the liver and, here, there was little difference between the sexes. In the testis there was N7-methylation of guanine in DNA, but no O6-methylguanine was detected.     

Muscle wasting after radiotherapy in young and adult rats

The impact of late muscular injury after radiotherapy on the well being of patients, particularly those treated at a relatively young age, is often underestimated. To extend the present knowledge, a detailed comparative study of the radiation response of skeletal muscles was performed. The hind limb of rats was irradiated at the age of 30-60 days (young), at approximately 200 days (adult) or at the age of >360 days (old), with single doses ranging from 15-60 Gy. Muscular wet weight, volume and tibia length was followed up to 12 months post-treatment. Radiation treatment resulted in muscular wasting, which was more severe at higher doses. The radiation response depended strongly on the age of the animal at the time of treatment. Radiation induced muscle wasting and stunted tibia growth were more prominent in young animals than in adult or in old rats. ED50 values based on normalized wet weight were 12.5 (11.5-13.6) Gy for young animals and 22.5 (21.8-23.3) Gy for adult animals. The gastrocnemius muscle of young animals appears to be more radiosensitive than the gastrocnemius muscle of adult or old animals. Furthermore, in young animals, severe wasting of the muscles may already occur after relative low radiation doses (single dose of 15 Gy).     

Liver and kidney tumors induced by N-nitroso-dimethylamine in Xenopus borealis (Parker)

N-nitroso-dimethylanine dissolved in aquarium water at a concentration of 400 ppm (1/4 of the LD50/30d) induced malignant tumors in 39 (54.2%) out of 72 young adult animals of the amphibian species Xenopus borealis. The first tumor was detected at 11 weeks, and the average latency was 35.1 weeks. Tumors were located in the liver (32 cholangiocarcinomas and 13 hepatocellular cancers) and the kidney (9 adenocarcinomas and 2 anaplastic cancers). Thirteen animals bore two or more types of tumors. These results demonstrate that a high percentage of tumors can be induced in amphibians by chemical carcinogens if appropriate methods are used.     

DNA Alkylation by Nitrosobis-(2-oxopropyl) amine in Rats of Different Ages

We have examined the methylation of liver DNA (O⁶- and N⁷-methylguanine) by nitrosobis-(2-oxopropyl)amine (BOP) in male and female rats at various ages, following treatment with 2.5 mg of BOP; this dose given twice weekly for 30 weeks induces tumors in all animals. Except in young rats there was more methylation in female rat liver than in male rat liver, when adjusted for different sizes of the animals. There were differences in the extent of methylation between young (4 weeks) and older rats, but not between young adult (20 weeks) and old adult (65 weeks) males; the latter developed liver tumors when treated with BOP, and the former did not. There was no obvious relation between increased susceptibility to liver tumor induction by BOP and the extent of alkylation of liver DNA. Methylation of DNA was lower in the kidney than in the liver and, here, there was little difference between the sexes. In the testis there was N⁷-methylation of guanine in DNA, but no O⁶-methylguanine was detected.     

Declining melatonin levels and MT1 receptor expression in aging rats is associated with enhanced mammary tumor growth and decreased sensitivity to melatonin

Serum melatonin (MLT) levels have been reported to diminish significantly by the 5th and 6th decades of life as the incidence of breast cancer increases. Given MLT’s anti-cancer activity, we hypothesize that age-related decline in pineal MLT production leads to enhanced breast cancer development and growth as women age. In this study, we sought to determine whether the growth of tissue-isolated mammary tumors in young, adult, and old female Buffalo rats relates to the age-related changes in MLT and its MT1 receptor. Significant decreases in the peak nighttime serum MLT levels were observed in old as compared to adult and young rats. Significantly diminished nighttime and early morning levels of MT1-melatonin receptors were observed in uteri from old rats compared to adult and young rats. Growth rates in transplanted, tissue-isolated, carcinogen-induced mammary tumors are significantly increased in old rats as compared to adult or young rats. The growth-suppressive actions of exogenous MLT are diminished in old rats compared to adult and young rats. This decrease in tumor response correlates with reduced expression of the MT1 receptor in old as compared to young and adult rats. Thus, enhanced mammary tumor growth is associated with old age and diminished levels of MLT and MT1 receptor during old age, resulting in reduced sensitivity to exogenous MLT. Finally, our studies demonstrate that the tissue-isolated tumor model is viable model system in which to study the role of aging on breast cancer growth.     

The relationship between urinary pyridinoline, deoxypyridinoline and bone metastasis in a rat breast cancer model

Background  Bone metastasis from breast cancer is often recognized clinically, but there are nonetheless several difficulties in diagnosis. In this study we used an animal model of bone metastasis from breast cancer and clarified the relationship between the urinary Pyd/Cr and Dpd/Cr and the progression of bone metastasis, compared with other bone related markers: serum alkaline phosphatase bone isozyme (ALP-BI), osteocalcin, and calcium. Methods  The evaluation of bone metastasis was assessed by histological examination of the thoracic and lumbar vertebrae. According to the histological findings 4 weeks after the tumor cell injection, 1 1 animals were retrospectively divided into 2 subgroups: (1) tumor-bearing rats with bone destruction due to bone metastasis (TBR-BD(+), n=5), (2) tumor-bearing rats without bone destruction (TBR-BD(-), n = 6). These animals were compared to age-matched controls without tumor cell injection (n=6). An additional 5 animals were sacrificed at 2 weeks after the tumor cell injection to evaluate micrometastasis to bone. Results  The values of other markers for bone metastasis in animals with micrometastatic foci in bone marrow did not differ significantly from those of the controls. Pyd/Cr and Dpd/Cr in the TBR-BD(+) group were significantly higher than those of the TBR-BD(-) and the control group (233 + 78.3 vs 93.8±6.5, 98.5±18.7, 123.1 ±35.9 vs 67.9±6.2, 60.6±9.8, p<0.01), while there were no significant differences between TBR-BD(-) and the control. Conclusions  Both Pyd/Cr and Dpd/Cr are correlated significantly with the volume of bone metastasis, and are useful for the diagnosis and evaluation of progression of bone metastasis compared with other markers.     

GGT reduction in beta carotene-inhibition of hamster buccal pouch carcinogenesis

Levels of activity for gamma glutamyl transpeptidase (GGT) were studied in hamster buccal pouches developing DMBA-induced epidermoid carcinomas and in pouches in which carcinogenesis was inhibited by topical application of beta carotene. The beta carotene acted to inhibit tumor development when applied topically on days alternate to the application of 0.25% DMBA in heavy mineral oil thrice weekly for 22 weeks. Forty male young adult Syrian hamsters were divided into four equal groups. Group 1 had DMBA applied to left buccal pouches thrice weekly. Group 2 had DMBA applied as in Group 1 but also beta carotene thrice weekly on days alternate to the DMBA application. Group 3 animals were painted with only beta carotene and Group 4 animals were untreated controls. The left buccal pouches were dissected at autopsy and divided in half. One half was fixed in formalin, sectioned in paraffin and stained with hematoxylin-eosin for histologic study. The other half was prepared for the histochemical demonstration of GGT activity using epithelial whole mount preparations. GGT activity was found to be reduced in the left buccal pouches of those animals treated with both beta carotene and DMBA when compared to those animals treated with DMBA alone.     

骨转移瘤患者尿羟脯氨酸水平检测的临床意义

目的　探讨骨转移瘤患者尿羟脯氨酸 (uHOP)水平测定在评估骨转移瘤患者病情进展与疗效中的价值。方法　对3 5例正常成人 ,2 0例原发肿瘤及 2 0例骨转移瘤患者的uHOP、血清AKP活性和Ca2 浓度进行检测 ,并进行比较和分析。结果　正常成人组uHOP水平为 ( 2 4.16± 9.91)mg/L ,原发肿瘤组为 ( 3 4.97± 18.5 4)mg/L ,两者无显著性差别 (P >0 .0 5 ) ;骨转移瘤组uHOP水平为 ( 67.5 8± 2 6.3 6)mg/L ,明显升高 ,与正常成人组及原发肿瘤组比较 ,均有非常显著性差异 (P <0 .0 1)。 结论　羟脯氨酸 (HOP)是骨胶原转换的特异性敏感指标。uHOP水平对鉴别骨转移瘤和监测病情有参考价值 ,uHOP水平检测是评估骨转移瘤的早期客观的检测手段之一     

Effect of host age on tumor-associated angiogenesis in mice.

Previous reports on the slower growth of tumors in senescent mice have suggested a decrease in tumor angiogenesis in these animals, but such an observation has not yet been documented quantitatively. In this study, we report the relative amount of tumor angiogenesis and tumor volume for two different types of tumor in 11 young (8-9-wk old) versus nine older (19-mo old) male C57BL/10 mice. B16 melanoma or SP1 methylcholanthrene-induced fibrosarcoma cells were injected into the ventral skin of mice. After 3 days, the mice were killed and the injection sites were examined for angiogenesis surrounding the tumor (centrally directed tumor angiogenesis), nerve-associated angiogenesis, and tumor volume. In the older mice, there was significantly less centrally directed tumor angiogenesis for both tumors tested, and nerve-associated angiogenesis was decreased for B16 melanoma. The mean tumor volume for the B16 implants was smaller for the older animals, but the mean SP1 tumor volumes were identical for both age groups. These findings support the hypothesis that tumor growth in older animals is associated with less formation of new blood vessels, and this may explain the slower tumor growth observed in aged animals with certain experimental tumors.     

Tumorigenicity of simian virus 40-transformed rat hepatocytes

Simian virus 40 (SV40)-transformed F344 rat hepatocytes were transplanted into newborn and normal and irradiated adult syngeneic F344 hosts. Three independently isolated SV40-transformed hepatocyte cell lines were inoculated s.c. into newborn syngeneic animals. One cell line, SV40hpl, produced tumors in two of 12 animals. Fixed tissue sections indicated that the tumors were relatively undifferentiated but had some epithelial cells and contained a peripheral mononuclear leukocyte infiltrate. Serum from a tumor-bearing animal tested by immunoprecipitation demonstrated antibodies to SV40 large-T- but not to small-t-antigen. A portion of one of the tumors was used to prepare the tumor cell line SV40hpl-1, which was 100% positive by immunofluorescence for SV40 nuclear T-antigen. In adult F344 rats subjected previously to whole-body irradiation, inoculation of SV40hpl-1 cells produced tumors in 83% of the animals. Continued passage of the tumor cell line in irradiated rats produced a tumor in one animal which paralyzed its host. The cell line derived from this tumor (SV40hpl-1-T1-2) was tumorigenic in nonirradiated adult hosts. The tumor cell lines were morphologically similar to each other but different from the SV40hpl-transformed cell line; the tumor cells contained less cytoplasm and grew to high densities in strings or multilayered foci without covering the dish surface. All tumor cells retained SV40 antigen expression, and at least one complete copy of the virus genome was retained through two passages in animals. We concluded that SV40 transformation of rat hepatocytes can produce a tumorigenic cell line. We have shown previously that SV40-transformed hepatocytes retain the ability to express proteins characteristic of adult differentiated liver. Development of this model system will enable us to examine expression of these proteins not only in transformed cells with tumorigenic potential but also in tumor tissue and transplantable tumor cell lines.     

The role of Wnts in bone metastases

Wnts are a large family of secreted glycoproteins that mediate bone development in the embryo and promote bone production in the adult. Autocrine Wnt signaling within tumor cells has been shown to promote tumorigenesis by enhancing tumor cell proliferation and survival. We recently demonstrated that prostate cancer cells (CaP) produce Wnts which act in a paracrine fashion to induce osteoblastic activity in CaP bone metastases. The ability of tumor-derived Wnts to influence bone development is regulated by multiple families of secreted antagonists including soluble frizzled related receptors (sFrp) and dickkopfs (DKK). CaP cells appear to produce DKK-1 early in the development of skeletal metastases, which masks osteogenic Wnts and thus favors an osteolytic environment at the metastatic site. As the metastases progresses, DKK-1 expression is lost allowing for a Wnt mediated osteoblastic response which predominates CaP boney lesions. Interestingly, blocking DKK-1 expression early in CaP metastasis prevents tumor establishment within the bone suggesting that osteolysis is a required first step in the development of CaP bone metastases. In this review, we discuss our data on the Wnt inhibitor DKK-1 in CaP bone metastasis in the context of current literature evidence that demonstrate that Wnt inhibitors can function as both tumor suppressors and tumor promoters. We provide a model that the affect of Wnt inhibitors on tumor development is dependent on the tumor micro-environment and suggest that DKK-1 is a switch which transitions CaP bone metastases from osteolytic to osteoblastic.     

Development of a xenograft glioma model in mouse brain

Xenograft intracerebral glioma models have been developed in normal mice by growing the rat C6 glioma in either adult or neonatal mouse brains. Using this tumor line it was possible to grow discrete intracerebral gliomas in either CBA or AKR adult mice or neonatal mice. The size of the tumor mass and length of survival was directly related to the number of tumor cells injected and the time after implantation. To obtain localized intracranial tumor growth cells were suspended in a 1% agarose solution before implantation. Following injection of 10(6) cells into the frontal lobe of adult CBA or AKR mice, discrete tumor masses greater than 4 mm in diameter were obtained in 90% of animals at 14 days, and the largest tumors in adult mice occurred between 21 and 28 days after implantation. The tumor size following implantation of 10(6) cells was significantly greater than with 10(5) cells at 7 days (P less than 0.05) and at 14 and 21 days (P less than 0.01). Less than 60% of mice of BALB/c, RIII, or C57 black strains developed tumors greater than 4 mm diameter at 14 days after intracerebral injection of 10(6) C6 cells. Using neonatal mice it was found that when 10(5) cells were injected intracranially tumors greater than 4 mm in diameter developed in 14 of 15 animals within 2 weeks (CBA mice). Similar results were seen in the RIII, AKR, C57 black, and BALB/c strains. Longer growth periods resulted in larger tumors, up to 8 mm in diameter (6 of 10 animals at 20 days). The tumors in the neonatal animals were not as discrete as in the adult mice, and tumor often spread to the meninges and into the lateral ventricles. The tumor harvested from the brain had a cloning efficiency of 1.2 +/- 0.4% (SD). A panel of monoclonal antibodies was raised to the C6 glioma, and this was used to define clearly the margins of the tumor within the brain. The xenograft mouse models should prove useful for the study of the therapy of gliomas.     

Diseases of renal function and bone metabolism after treatment for early onset cancer: A registry-based study

Modern cancer therapy has led to a growing number of pediatric and young adult cancer survivors, who are prone to increased morbidities caused by the late effects of therapy. The aim of our study was to investigate pediatric and young adult cancer survivors' morbidity due to renal and bone metabolism diseases and especially to study bone metabolism in cancer survivors with renal disease. Patients were identified from the Finnish Cancer Registry, and the cohort consisted of 13,860, 5-year survivors of cancer diagnosed below the age of 35 years. Healthy siblings were used as the comparison cohort. Information on the main outcomes was linked from the national Care Register for Health Care. Hazard ratios (HRs) comparing cancer survivors to siblings were calculated for various outcomes. The patient cohort was separated into two age groups, pediatric (0–19 years) and young adults (20–34 years). Significantly elevated HRs (p < 0.0001) in survivors were observed in both age groups for scoliosis (HR 1.6, 95% confidence interval [CI] 1.3–2.0), osteoporosis (HR 5.2, 95% CI 2.4–11.4), osteonecrosis (HR 12.7, 95% CI 5.4–29.7), nephritis (HR 1.9, 95% CI 1.5–2.2) and kidney failure (HR 3.6, 95% CI 2.4–5.3) for all. For cancer survivors with a renal outcome, the risk for developing any outcome of bone metabolism was increased (HR 2.3, 95% CI 1.4–3.6). These results show that pediatric and young adult cancer survivors have an elevated risk for long-term, adverse outcomes related to renal function and bone metabolism. These results suggest follow-up care for young cancer patients.     

Combination chemotherapy involving alpha-difluoromethylornithine and 1-beta-D-arabinofuranosylcytosine in murine L1210 leukemia

Administration of 2% aqueous alpha-difluoromethylornithine (DFMO) as the sole drinking-fluid to C57BL X DBA/2 F1 (hereafter called BD2F1) mice for 5 days resulted in significant reduction of labeling index, percentage of cells in S phase, and intracellular putrescine and spermidine concentrations of bone marrow cells. DFMO treatment also resulted in moderate leukopenia. The decreases in body weight, peripheral leukocyte and erythrocyte counts, and subsequent recovery following administration of 1-beta-D-arabinofuranosylcytosine (ara-C), an S-phase-specific cytotoxic agent, to animals receiving DFMO was comparable to those observed in animals which received ara-C alone. In animals inoculated i.p. with L1210 cells, DFMO treatment produced a marginal increase in survival time and significant reductions in putrescine and spermidine concentrations of the tumor cells. However, in contrast to normal bone marrow cells, depletion of polyamines in tumor cells resulted in the progressive accumulation of these cells in S phase; by Day 5 following DFMO treatment, greater than 70% of the tumor cells were found to be in S phase compared to only 55% for cells from untreated animals. A significant synergistic increase in survival time with a combination of DFMO and ara-C was observed when the ara-C therapy was initiated at the time of maximum accumulation of tumor cells in S phase. The implications of these findings for the management of neoplasia are discussed.     

Reproducibility and relation to specific and non-specific anti-tumor resistance of the tumor "sneaking through" phenomenon.

The reproducibility and immunological specificity of the tumor "sneaking through" phenomenon and enhancement of tumor growth were studied in syngeneic and random-bred Syrian hamsters by means of a quantitative modification of the transplantation test. After primary challenge the phenomenon was neither observed in normal animals nor in animals effectively immunized against tumor. However, it was regularly observed in some "immune" animals after secondary challenge. In primary challenge of animals "sneaking through" phenomenon was most often observed in animals pretreated with large doses of heat-inactivated tumor cells. This characteristic could not be transferred with serum of pretreated animals. In contrast to specific tumor immunity, the "sneaking through" pbenomenon appeared to be immunologically non-specific. This was observed in cross-transplantation tests with tumor cells bearing different TSTAs. Thus, TSTA is not an inducer and apparently not a target for a response leading to enhancement of tumor growth in pretreated hamsters. Experiments demonstrating enhanced tumor growth in pretreated animals at the same time demonstrate two other possibly more essential findings: (1) normal animals are naturally resistant to transplantation of 1 to about 1 x 10(3) (or more) tumor cells; and (2) this resistance can be totally abrogated by the pretreatment of normal animals with tumor cell preparations. The preliminary data demonstrate that abrogation of natural anti-tumor resistance in adult hamsters subsequently inoculated with SV40 leads to rapid development of primary tumors in such animals. The development of specific anti-tumor immune response in animals treated with inactivated tumor cell preparations was also studied. Significant non-specific inhibition of sponse in Syrian hamsters treated with inactivated syngeneic tumor cells was observed. The data obtained are considered to demonstrate two anti-tumor defense systems in the animal, i.e., non-specific natural resistance and specific anti-tumor immunity. The first seems to be responsible for elimination of low numbers of tumor cells in the normal organism and also to be esseitial for effective induction and functioning of the specific anti-tumor immunity.     

Stimulation of tumor growth in adult rats in vivo during acute streptozotocin-induced diabetes

The effects of acute diabetes mellitus on the growth of Morris hepatoma 7288CTC and Jensen sarcoma were studied in fed, young (less than 200 g), and adult (greater than 250 g) rats. Animals were matched for tumor size and growth; the rates of tumor growth were the same in fed, young and adult nondiabetic rats. Diabetes was induced by the i.v. injection of streptozotocin (65 mg/kg total body weight) into tumor-bearing rats and changes in arterial blood nutrient concentrations were compared to changes in the rates of tumor growth and DNA synthesis. In young rats acute diabetes did not increase the blood concentrations of the fat store-derived nutrients and did not increase the rate of tumor growth. In adult rats, however, acute diabetes raised the arterial blood free fatty acid, glycerol, triglyceride, and ketone body concentrations to high levels and increased the rate of tumor growth about three times over that observed in untreated rats. Progress curves for the mobilization of host fat stores and for incorporation of [methyl-3H]thymidine into tumor DNA during the onset of diabetes showed that these activities were closely correlated in adult rats. Both processes began to increase 2 to 4 h after streptozotocin treatment, reached an initial peak at 12 to 16 h, decreased to a low point at 18 to 20 h, and then increased again to the new steady state after 23 to 24 h. The results indicate that the rate of tumor growth in rats in vivo is limited by the availability of a substance(s) present in the hyperlipemic blood of adult diabetic rats. The tight relationship between host lipolysis and tumor growth suggests that the substance(s) is derived from host fat stores.