Oncofetal protein accompanying irradiation-induced small-bowel adenocarcinoma in the rat.

A tumor-associated protein was found in tissue derived from an X-irradiation-induced adenocarcinoma in the small bowel of the rat. The protein was associated with the cell membranes of the tumor tissue. It shared common antigenic determinants both with a rat fetal protein and a perchloric acid-soluble protein isolated from the serum of the tumor-bearing rat.

Lung tumorigenic response of strain A mice exposed to hypoxic cell sensitizers alone and in combination with gamma-radiation.

The influence of metronidazole, misonidazole, and desmethylmisonidazole on the induction of lung adenomas in the strain A mouse was examined. Two dose levels of the hypoxic cell sensitizers, 0.2 and 0.6 mg/g, were used either alone or in combination with 900 rads of gamma-radiation in a fractionated dose schedule of twice a week for 3 weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased (p less than 0.10) in the group receiving the higher dose (0.6 mg/g) of misonidazole but was not significantly different from results for the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with that in the control group. Thus, under the experimental exposure conditions used in this investigation, which were somewhat similar to the exposure conditions occurring in clinical treatment, each of the hypoxic cell sensitizers tested failed to sensitize significantly the mice to the carcinogenic effects of gamma-radiation.

Alterations in Langerhans cells and Thy-1+ dendritic epidermal cells in murine epidermis during the evolution of ultraviolet radiation-induced skin cancers.

To understand the role of cutaneous immune cells in host resistance to the induction and growth of skin cancer, we investigated the number and morphology of murine dendritic epidermal cells (dEC) during the evolution of ultraviolet (UVA) UV-induced skin cancers. Female C3H/HeN mice were treated topically with 8-methoxypsoralen followed by ultraviolet A (UVA) radiation 3 times/week or irradiated with UVB radiation 3 times/week. In both psoralen plus UVA- and UVB-treated mice, ATPase+ and Ia+ Langerhans cells almost completely disappeared from the treated skin during the early latency period of tumor development (4 weeks) but reappeared in the epidermis late in the latency period (between 15 and 22 weeks). The ATPase+ cells that reappeared in the epidermis had a rounder, less dendritic morphology than normal Langerhans cells. Thy-1+ dEC were totally depleted from the epidermis in both treatment groups at the end of first week of treatment and were nearly absent from the skin during the entire latency period. After tumors appeared (29 weeks), Thy-1+ dEC were still absent or detected only in small numbers in skin surrounding the tumors. ATPase+ and Ia+ cells present in skin around the tumors constituted 60 to 80% of the number in nonirradiated skin. Mice that received UVA radiation alone developed no tumors. ATPase+ and Ia+ Langerhans cells and Thy-1+ dEC were detected in UVA-treated epidermis after 22 weeks and 43 weeks, although the numbers were lower than those in unirradiated mice. Most psoralen plus UVA-induced tumors (81%) were squamous cell carcinomas, whereas only 24% of UVB-induced tumors were of this histological type. Our results demonstrate that UV-induced skin cancers developed in the presence of ATPase+ and Ia+ cells in the epidermis and in the absence of Thy-1+ dEC.

NMR study of in vivo RIF-1 tumors. Analysis of perchloric acid extracts and identification of 1H, 31P and 13C resonances.

Perchloric acid extracts of radiation-induced fibrosarcoma (RIF-1) tumors grown in mice have been analyzed by multinuclear NMR spectroscopy and by various chromatographic methods. This analysis has permitted the unambiguous assignment of the 31P resonances observed in vivo to specific phosphorus-containing metabolites. The region of the in vivo spectra generally assigned to sugar phosphates has been found in RIF-1 tumors to contain primarily phosphorylethanolamine and phosphorylcholine rather than glycolytic intermediates. Phosphocreatine was observed in extracts of these tumor cells grown in culture as well as in the in vivo spectra, indicating that at least some of the phosphocreatine observed in vivo arises from the tumor itself and not from normal tissues. In the 31P-NMR spectra of the perchloric acid extract, resonances originating from purine and pyrimidine nucleoside di- and triphosphate were resolved. HPLC analyses of the nucleotide pool indicate that adenine derivatives were the most abundant components, but other nucleotides were present in significant amounts. The 1H and 13C resonance assignments of the majority of metabolites present in RIF-1 extracts have also been made. Of particular importance is the ability to observe lactate, the levels of which may provide a noninvasive measure of glycolysis in these cells in both the in vitro states. In addition, the aminosulfonic acid, taurine, was found in high levels in the tumor extracts.

UVB-induced collagen changes in the skin of the hairless albino mouse.

Biochemical techniques have been used to measure ultraviolet-B (UVB)-induced changes in dermal collagen composition. Hairless albino mice were irradiated dorsally with a daily dose of 62 mJ/cm2 UVB for 12, 24, 30, and 36 weeks. Nonirradiated controls were housed under identical conditions. Additional groups were irradiated for similar periods and kept for a further 6-24 weeks without irradiation. Skin samples were taken from dorsal and ventral (nonirradiated) surfaces and types I and III collagen were quantified densitometrically after cyanogen bromide digestion and polyacrylamide gel electrophoresis. Type III collagen was expressed as a percentage of the total types I and III collagen and the ratio of dorsal/ventral type III (D/V III) was determined for each mouse. The ratio increased significantly in irradiated animals whereas it decreased in the corresponding period in control animals. In irradiated mice withdrawn from UV exposure the ratio D/V III tended to revert to control levels. These data are in agreement with those of our previous human studies, which showed an increase in type III collagen in sun-exposed skin when compared with covered sites.

Postirradiation malignant fibrous histiocytoma expressing cytokeratin. Implications for the immunodiagnosis of sarcomas.

A malignant fibrous histiocytoma of the sacrum complicating the course of radiation therapy for endometrial carcinoma is presented. Although the tumor fulfilled the clinical, radiologic, and histologic criteria for a postirradiation malignant fibrous histiocytoma of bone, it also expressed cytokeratin. That this immunoreactivity reflected keratin synthesis by the tumor and not an unusual pattern of cross-reactivity with another intermediate filament such as vimentin is strongly suggested by the reproducibility of the immunoreactivity utilizing both polyclonal and monoclonal antibodies and extinction of the immunoreactivity following absorption of the primary antiserum with keratin proteins. This is the first reported instance of keratin expression by a malignant fibrous histiocytoma; it indicates that sarcomas apart from synovial sarcoma and epithelioid sarcoma may sometimes express this protein.

Mammary carcinogenesis in Sprague--Dawley rats following 3 repeated exposures to 14.8 MeV neutrons and steroid receptor content of these tumor types.

166 Sprague-Dawley Rats (148 males and 118 females) submitted to different hormonal conditions were exposed to 3 repeated whole-body irradiations of 14.8 MeV neutrons or sham-irradiated between 50 and 65 days of age (total absorbed doses: 3 x 2 rad and 3 x 8 rad). They were observed for 11 months. In the male group, a small number of tumors was obtained. In the female group, 75 breast neoplasms were scored in 41 of 78 irradiated animals (54 fibroadenomas, 20 adenocarcinomas and 1 fibrosarcoma). A second group of benign and malignant tumors was observed from 200 days on. The neoplastic response to fast neutron fractionated irradiations was increased by pregnancy with subsequent lactation. Estradiol and progesterone receptors were measured in 34 tumor samples. Fibroadenomas (1;5) and adenocarcinomas (1;3) bound labelled steroids. Like in human breast cancer metastases, steroid receptors are found in recurrences only if present in the primary tumor.

DNA content in radiation-associated thyroid cancer.

DNA content has been reported to be of prognostic significance in differentiated thyroid carcinoma. Since malignant tumors with irradiation as an initiator often contain DNA aberrations, the DNA content of well-differentiated thyroid carcinoma in patients with a prior history of low-dose head and neck irradiation was determined and compared with similar nonradiation-associated lesions. The DNA content of thyroid cancers from 53 patients was determined with use of flow cytometry. Sixteen radiation-associated thyroid carcinomas (11 papillary, 3 follicular, and 2 medullary) all were diploid. In a group of 37 nonradiation-associated tumors, 10 were aneuploid (10 of 29 papillary carcinomas and 0 of 2 follicular or 6 medullary carcinomas). This difference in DNA content is significant (p less than 0.02, Fisher's exact test). These findings were unexpected and suggest that if the initiating irradiation causes a DNA aberration, this aberration is not reflected in DNA content as measured by means of flow cytometry.

Glycosphingolipids in murine lymphocytes from thymus and spontaneous and X-ray induced thymomas.

Lymphocytes from spontaneous thymoma in AKR mice and from X-ray induced thymoma in C57B1/6 mice showed elevated levels (by 50% and 100%, respectively) of lipid-bound sialic acid as compared with lymphocytes from normal thymuses used as controls. Some ganglioside fractions in thymomas were elevated 4-6-fold over those in normal thymuses while other fractions decreased or disappeared. Neutral glycosphingolipid (NGSL) content in lymphocytes from thymomas was also changed. Thin-layer chromatography of NGSLs showed that the fractions migrating as ceramide monohexoside (CMH), dihexoside (CDH) and below globoside standards were increased, respectively, 2-3-fold, 3-6-fold and 2-fold in both types of thymomas. Methylation and gas-liquid chromatography analysis confirmed the presence of CMH, CDH and globoside in NGSLs isolated from X-ray induced thymoma.

A novel form of GD1c ganglioside IV3 (NeuAc alpha 2-8 NeuGc)Gg4Cer from murine X-ray induced thymoma.

Four disialoganglioside fractions were isolated from X-ray induced thymoma in C57Bl/6 mice. On the basis of compositional and methylation analyses as well as degradation with specific exoglycosidases a novel form of GD1c ganglioside NeuAc alpha 2-8 NeuGc alpha 2-3 Gal beta 1-3 GalNAc beta 1-4 Gal beta 1-4 GlcCer was identified.

The U.S. Transuranium Registry report on the 241Am content of a whole body. Part I: Introduction and history of the case.

The first whole-body analysis of the U.S. Transuranium Registry was initiated in 1979. The donor was a 49-yr-old male Caucasian radiochemist who died of metastatic malignant melanoma. The donor had a recognized, longstanding 241Am internal deposition first identified in a routine urine sample in 1958. A summary of the clinical and postmortem findings is presented with the chronologic sequence of the procedures.

The U.S. Transuranium Registry report of the 241Am content of a whole body. Part IV: Preparation and analysis of the tissues and bones.

Los Alamos National Laboratory has analyzed autopsy tissue for the USTR, as a part of its study of the uptake, distribution and retention of Pu and other transuranic elements in occupationally exposed workers since 1978. In April 1979, Los Alamos received the internal organs and bone samples from the first whole-body donation to the USTR. The donor was known to have an internal deposition of 241Am. All soft tissue, the bones from the right half of the skeleton, and the odd-numbered vertebrae were received at Los Alamos in February 1980. The bones were subdivided along anatomical areas of interest. All soft tissues and bone specimens were analyzed for their 241Am content. A total deposition of 147.4 nCi 241Am was measured. Approximately 18% of the 241Am remaining in the body (disregarding that in the left hand), was found in the soft tissues, and 82% was in the bones and teeth. The soft tissues and organs containing the largest amounts of 241Am were the combined soft tissue (striated muscle, connective tissue and skin) 8.8%; liver, 6.4% and respiratory tract, 1.5%. The remaining organs accounted for 0.9% of the systemic burden.

[Common proviral integration sites in C57BL mouse lymphoma induced by mouse radiation leukemia virus and absence of novel proviral sequences in DNA from radiation-induced lymphoma]. / Sites communs d'intégration de provirus dans les lymphomes induits chez des souris C57BL par le virus des radioleucoses murines (RadLV) et absence de nouvelles séquences provirales dans l'ADN des lymphomes radio-induits.

Radiation leukemia virus (RadLV)-induced lymphomas of C57BL mice display the appearance of novel proviral sequences at common sites of their DNAs. These results are compatible with the hypothesis of viral oncogenesis by promotor insertion. Radiation-induced tumors do not acquire detectable novel provirus, suggesting that activation of a transforming gene proceeds by a mechanism distinct from the former.

Carcinogenesis and ageing--VII. Carcinogenic effect of single total-body X-ray irradiation in young and old female rats.

Female rats aged 3 and 14 months were exposed to single X-ray irradiation at a dose of 4 Gy. Total frequency of neoplasms and that of malignant tumors in the younger age group amounted to 78 or 42%, and in the older age age group to 66 and 31% respectively, while in the corresponding age groups the figures were as follows: 48 or 7% (p less than 0.05). The comparative analysis of the carcinogenic effect of irradiation in young and old rats has revealed that sensitivity of the mammary gland epithelium, ovarian tissue and thyroid epithelium to malignant actions of irradiation decreases with age. The paramount importance in modification of tissue sensitivity to carcinogenic action of irradiation in ageing is suggested to be related to age-dependent changes in the proliferative activity of the target tissues.

Induction of mouse mammary tumor virus RNA in mammary tumors of BALB/c mice treated with urethane, X-irradiation, and hormones.

The involvement of mouse mammary tumor virus (MTV) in the development of mammary tumors of nonviral etiology in BALB/c mice was studied by measuring the levels of MTV RNA, MTV DNA, and MTV proteins in spontaneously arising and hormonally, chemically, and/or physically induced mammary tumors of BALB/c females. The following results were obtained. (i) Spontaneous mammary tumors contained very low levels of MTV RNA; 4 X 10(-6)% of the the cytoplasmic RNA was MTV RNA. No MTV proteins could be demonstrated by using sensitive radioimmunoassays for MTV proteins p27 and gp52. (ii) Mammary tumors induced by treatments with urethane or X-irradiation alone contained higher levels of MTV RNA; these tumors contained 3- and 19-fold more MTV RNA, respectively, compared with spontaneous mammary tumors. (iii) Mammary tumors induced by combined treatment with urethane and X-irradiation expressed high levels of MTV RNA in the mammary tumors; a 1,724-fold increase in MTV RNA content compared with spontaneous mammary tumors was observed. However, very low levels of MTV proteins gp52 and p27 were detected, suggesting some kind of impairment at the translation of the MTV RNA. MTV RNA was also induced by this treatment in mammary glands and spleens, but not in the livers of tumor-bearing animals. (iv) Balb/c females continuously exposed to prolactin contained high levels of MTV RNA and MTV proteins in stimulated mammary glands and in the hormonally induced mammary tumors. These findings suggest that MTV is not responsible for the maintenance and probably also not for the development of all murine mammary cancers.

Lung cancer in a Thorotrast administered patient.

A 79-year-old man developed small cell carcinoma in the lung 43 years after Thorotrast-injection. The tumor with interstitial fibrosis arose in the periphery of the lung. Thorotrast particles were observed in the liver, spleen, bone marrow, and lymph nodes but not in the lungs. Four other Japanese cases of lung cancer after Thorotrast injection were reviewed.

Basement membranes in ultraviolet light-induced skin lesions and tumors.

Basement membrane changes in human skin exposed to UV irradiation were studied by light and electron microscopy and antibodies to human collagen IV and laminin were compared to similar lesions in non-sun-exposed areas. A distinct basement membrane was seen in cases of epidermal solar keratosis, even with marked dysplasia and Bowenoid type lesions, and also around most of squamous cell carcinomas which showed basement membrane irregularities, thickening and reduplication. The invading edges of the squamous cell carcinomas with inflammatory infiltrates were devoid of laminin and collagen. Basement membrane disruption was also observed in lichen planus-type solar keratosis with severe inflammation, but with no evidence of malignancy. Alterations in basement membrane structure and location were associated with cutaneous morphological abnormalities not due to UV irradiation as such.

Etiologic related studies of ultraviolet light-mediated carcinogenesis.

Comparisons were made of cholesterol-5alpha, 6alpha-epoxide (CAE) levels in skin of hairless mice maintained on a regular or antioxidant supplemented diet and receiving chronic ultraviolet light (UVL) radiation over an 18-week period. Cholesterol-5alpha, 6alpha-epoxide levels in skin of animals on antioxidant supplemented diet, while reaching a peak four weeks after that of animals on regular diet, thereafter were consistently higher. Dietary antioxidants nevertheless had an inhibitory effect on UVL-induced tumors. These data are inconsistent with the theory of CAE involvement as an ultimate carcinogen in UVL-mediated carcinogenesis.