Pathological characteristics of thyroid glands from Japanese Black Cattle living in the restricted area of the Fukushima Daiichi Nuclear Power Plant accident.

To study the effect of ionizing radiation on thyroid glands, 66 Japanese Black cattle residing in the restricted area of the Fukushima Daiichi Nuclear Power Plant in 2013-2017 were pathologically examined. There were no clinical symptoms of thyroid disease in these cattle. Three cases of goiter and seven of atrophy were found in two among the four farms examined. Cases of goiter exhibited normal morphological structure without mass or nodule formation in thyroid glands. Cellular atypia or capsular invasion of the follicular epithelium was absent. The estimated integrated dose of external radiation in goiter cases ranged from maximum 797 mSv to minimum 24 mSv. All lobules in the seven atrophic thyroid glands were affected, but pathological findings, such as inflammatory cell infiltration or stromal fibrosis, were not observed. The estimated integrated dose of external radiation in atrophic thyroids ranged from maximum 589 mSv to minimum 8 mSv. Immunohistochemical analysis of anti-nitroguanosine and the TUNEL method in goiter and atrophic thyroid glands did not reveal any positive findings. The present study indicates that there was no significant relationship between a radiation effect and pathological findings in any thyroid glands.

Retrobulbar lymphoma associated with a ballistic foreign body in a cat.

A seven-year-old domestic shorthair cat, adopted 5 years previously with a corneal perforation of the left eye, was presented for investigation of a left orbital mass. Computed tomography revealed a metallic foreign body within a contrast-enhancing, heterogeneous orbital mass. Large cell lymphoma was diagnosed from a fine needle aspirate. The cat staged negatively and was treated with L-asparaginase, prednisolone and three fractions of radiation therapy. A rapid clinical remission was obtained and the cat remained in remission for 3 years after therapy. This is the first report of large cell lymphoma likely occurring secondary to a foreign body.

Incidence of acute myeloid leukemia and hepatocellular carcinoma in mice irradiated with 1 GeV/nucleon (56)Fe ions.

Abstract Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the leukemogenic efficacy of one such HZE species, 1 GeV (56)Fe ions, a component of space radiation, in a mouse model for radiation-induced acute myeloid leukemia. CBA/CaJ mice were irradiated with 1 GeV/nucleon (56)Fe ions or (137)Cs gamma rays and followed until they were moribund or to 800 days of age. We found that 1 GeV/nucleon (56)Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia (AML). However, (56)Fe-ion-irradiated mice had a much higher incidence of hepatocellular carcinoma (HCC) than gamma-irradiated mice, with an estimated RBE of approximately 50. These data suggest a difference in the effects of HZE iron ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis.

Osteoradionecrosis and radiation induced bone tumors following orthovoltage radiation therapy in dogs.

Osteoradionecrosis and radiation-induced bone tumors are rare complications of radiation therapy. Little information regarding these complications is available in veterinary medicine. We characterized these complications and investigated risk factors in 119 dogs (122 sites) that received definitive orthovoltage radiation therapy to appendicular sites. Long-term survival was expected in all dogs. The complications of interest were osteoradionecrosis and secondary bone tumor, evaluated radiographically, histopathologically, or both. Complication rates were estimated using the Kaplan-Meier product-limit method, and Fisher's exact test or chi-square test was used to compare the complication rate. The median survival time was 1405 days, with median follow-up duration of 657 days. There were 10 radiation-induced bone tumors and five radiation-induced fractures, with two dogs developing both, for an overall complication rate of 11%. The latent period ranged from 1.2 to 6.4 years for osteoradionecrosis and from 2.6 to 8.7 years for radiation-induced bone tumor. Complications were significantly higher in the humerus (P < 0.0001), and in dogs younger than 7 years (P = 0.014). Similar assessment of complications in dogs irradiated with megavoltage photons or electrons are needed.

Modeling lung cancer incidence in rats following exposure to radon progeny.

Lung cancer incidence in Sprague-Dawley rats was simulated by a biologically based carcinogenesis model, which is formulated mathematically in terms of a stochastic state-vector model. Doses to the sensitive target cells in the bronchial epithelium of the rat lung were calculated by a stochastic dosimetry model, considering the distinct monopodial branching structure and the crossfire of alpha particles from alveolar tissue to bronchial epithelium. Bronchial and alveolar cellular doses could reasonably be approximated by lognormal distributions, with geometric standard deviations (GSD) between 7 and 10, depending on exposure conditions. Based on a dose-exposure conversion factor of 8.5 mGy WLM(-1) and a GSD of 8, lung cancer incidences were calculated for each cumulative exposure category in the rat inhalation study, consisting of different exposure rates and exposure times. The fair agreement between theoretical predictions and experimental data over the whole exposure range emphasises the necessity to incorporate the full cellular dose distributions rather than their mean values.

Search for a genetic link for mammary cancer in a beagle colony.

BACKGROUND: A possible genetic link for malignant mammary tumor (MMT) was investigated. MATERIALS AND METHODS: Records of an internally-irradiated beagle colony followed from the early 1950's until about 1995 were searched and analyzed by standard statistical procedures. RESULTS: Only a single ancestor yielded a "p" value (Fisher's Exact Test) for an overrepresentation among descendants with MMT at < 0.025 (one-sided test), and the number of comparisons for the 169 ancestors where the relative fraction of animals with MMT was greater than that for non MMT dogs (61) suggests that this could have occurred by chance alone. Results of other statistical tests were not remarkable. CONCLUSION: No genetic link for MMT in this colony could be established with the available data. These findings may or may not be relevant to humans.

Malignant tumor formation in dogs previously irradiated for acanthomatous epulis.

In this retrospective study of 57 dogs irradiated for oral acanthomatous epulis, 2 (3.5%) dogs developed a second tumor (sarcoma, osteosarcoma) in the radiation treatment field at 5.2 and 8.7 years after the end of radiation therapy. As opposed to previous reports, no second epithelial tumors developed in the radiation treatment field. There is a risk of radiation-induced carcinogenesis, but it appears that it is a relatively low risk and an event that occurs years after radiation therapy. Radiation-induced tumors are of more concern in younger dogs that undergo radiation therapy for tumors that are radioresponsive, such as acanthomatous epulis, where long-term survival is expected. The only statistically significant variable in the survival analysis was age, with dogs less than 8.3 years old having a significantly longer median overall survival (2322 days) than dogs older than 8.3 years (1106 days; P<0.0001).

Radiation-induced glioblastoma multiforme in two adult baboons (Papio cynocephalus anubis).

A diagnosis of glioblastoma multiforme (GBM) was made for cerebral masses found at necropsy in two baboons (Papio cynocephalus anubis). Case 1 was an adult (6.18 years old) male baboon that suddenly died during a physical examination as part of a clinical evaluation for a leg lameness. Case 2 was an adult (5.95 years old) female baboon that stopped breathing during anesthesia for an magnetic resonance imaging to evaluate lethargy, weight loss, inappetence, and dilated pupils. Both animals had undergone total body irradiation with cobalt during a research protocol. The incidence of spontaneous brain tumors in nonhuman primates is low, but radiation-induced GBM lesions in rhesus macaques (Macaca mulatta) have been reported. A definitive diagnosis was made in these cases, using histopathologic criteria of cellular pleomorphism, high mitotic rate, regions of coagulation necrosis, and endothelial proliferation.

Radiation induced vertebral osteosarcoma following treatment of an intradural extramedullary spinal cord tumor in a dog.

A 2-year-old neutered female Rottweiler diagnosed with an intradural extramedullary spinal cord tumor at T12-T13 was successfully treated with cytoreductive surgery followed by Cobalt 60 teletherapy. The dog was euthanised 5-and-a-half years later following diagnosis of an osteosarcoma involving the L1 and L2 vertebrae. Evidence of the initial tumor was not present at necropsy. The vertebral neoplasm fulfilled all of the accepted criteria for a radiation induced tumor. It was concluded that adjunctive irradiation should be considered for treatment of intradural extramedullary tumors of young dogs when total surgical resection is not possible. Although tumor induction is a rare late effect of radiation therapy, the risk of this occurrence should be considered when irradiating young animals. Radiation induced tumors in dogs have been associated with coarse fractionation schemes, or when large intraoperative doses have been administered. A lower dose per fraction, e.g., 3 Gy/fraction or less, is advisable when irradiating young dogs or any dog in which the life expectancy is 3-5 or more years after irradiation.

Classification and behavior of canine mammary epithelial neoplasms based on life-span observations in beagles.

As part of a study of the effects of low-level radiation, 1,343 Beagles, including 671 males and 672 females, were evaluated over their full lifetime for the occurrence of mammary neoplasia; there were 139 control males and 138 control females and 532 irradiated males and 534 irradiated females. All nodules found in surgical specimens or at necropsy were evaluated histologically. The overall incidence, metastasis and recurrence rates, and contribution to mortality of mammary neoplasms were determined. Based on this unique opportunity to correlate morphologic characteristics with ultimate biological behavior of all mammary tumors in a defined canine population, we propose a histogenetically based reclassification of epithelial mammary tumors. Of the 672 female dogs, 70.8% (476) had at least one mammary neoplasm; 60.7% (408) had more than one. Two male dogs had mammary neoplasms. Of 1,639 mammary carcinomas in the 672 females, 18.7% (307) were classified as ductular carcinomas (arising from the small interlobular or intralobular ductules), whereas 80.7% (1,322) were classified as adenocarcinomas of other histogenetic origin. Of 73 fatal carcinomas, ductular carcinomas accounted for 48 fatalities (65.8%), whereas other adenocarcinomas accounted for only 20 fatalities (27.4%). Radiation had no effect on this ratio. Ductular carcinomas also had a higher rate of metastasis than did adenocarcinomas. Existing classifications of mammary carcinomas do not recognize the characteristic morphologic features, the degree of malignancy, and the prognostic importance of these ductular carcinomas. Metastasis rates did not differ between simple and complex carcinomas or between those lesions and adenocarcinomas in mixed tumors. True carcinosarcomas metastasized more frequently (100%, or 5/5) than did adenocarcinomas in mixed tumors (34.4%, or 22/64), emphasizing the importance of not lumping these tumors under the classification of malignant mixed tumors.

The physiologic response of domestic animals to ionizing radiation: a review.

With respect to clinical signs of the radiation syndromes, some remarkable species variations exist. For example the marked delayed reaction of the acute hematologic response in cows. An unusually high sensitivity of the central nervous system is found in burros, which is probably caused by acute vascular and/or metabolic changes in the brain. The species-specific number of intestinal crypt and hemopoietic stem cells may explain the early survival differences among species after high doses of irradiation. Mortality due to acute radiation syndromes is lowest in chickens. Regarding late effects, various neoplasms are typical in dogs, and cattle more commonly develop cataracts.

[Chronic damage in domestic animals after ionizing radiation (review)]. / Chronische Schäden bei Haustieren nach Einwirkung ionisierender Strahlung (Ubersichtsreferat).

Late effects have to be taken into account after survival of high doses of ionizing radiation, after protracted and fractionated exposure as well as after radiotherapy. In this respect species specific peculiarities become apparent. In burros, e.g., late effects after high dose of acute radiation exposure comprised shortening of lifetime. While in this species no tumors were seen, squamous-cell carcinoma around the eyes, in the skin above the sacral region and withers became apparent in cattle. Dogs developed tumors of different localisation, type and dignity after pre- and postnatal exposure. Cataracts appeared in cattle. Primarily, early cardiac failure (myocardial atrophy, fibrosis of the pericardial sac) was seen in chicken. After protracted and fractionated exposure especially the pig showed an exceptional tolerance. Late effects of the skin (atrophy), liver (degeneration), kidney (fibrosis) and nerves (neuropathy) were described in particular for dogs and pigs.

Relationship of natural incidence and radiosensitivity for bone cancer in dogs.

A comparison of the risk coefficients for 239Pu- or 226Ra-induced bone cancer in two canine breeds, one with a relatively low (beagle) and the other with a very high (St. Bernard) natural incidence, indicated only slightly higher risk in the giant breed. The differences in risk for skeletal malignancy in 239Pu and 226Ra dogs were nonsignificant (p > 0.05). Likewise, the values of the 239Pu:226Ra "toxicity ratios" for these respective breeds, using bone cancer as the endpoint, were not significantly different at the 0.05 level. The anatomical distribution of the radiation-induced bone tumors tended to be a function of both the bone mass and the skeletal distribution of the radionuclide, not the site of predilection for naturally occurring bone neoplasia. Although the etiology of the higher natural incidence of bone cancer in the St. Bernard was not determined, several possible factors, including a higher osteoblastic activity level in the St. Bernards, are presented. These data suggest that making extrapolations of radiation-induced bone cancer risk from animals to humans is valid.

A CDKN2-like polymorphism in Xiphophorus LG V is associated with UV-B-induced melanoma formation in platyfish-swordtail hybrids.

The genetic basis of spontaneous melanoma formation in spotted dorsal (Sd) Xiphophorus platyfish-swordtail hybrids has been studied for decades, and is adequately explained by a two-gene inheritance model involving a sex-linked oncogene, Xmrk, and an autosomal tumor suppressor, DIFF. The Xmrk oncogene encodes a receptor tyrosine kinase related to EGFR; the nature of the DIFF tumor suppressor gene is unknown. We analyzed the gentic basis of UV-B-induced melanoma formation in closely related, spotted side platyfish-swordtail hybrids, which carry a different sex-linked pigment pattern locus, Sp. We UV-irradiated spotted side Xiphophorus platyfish-swordtail backcross hybrids to induce melanomas at frequencies 6-fold higher than occur spontaneously in unirradiated control animals. To identify genetic determinants of melanoma susceptibility in this UV-inducible Xiphophorus model, we genotyped individual animals from control and UV-irradiated experimental regimes using allozyme and DNA restriction fragment length polymorphisms and tested for joint segregation of genetic markers with pigmentation phenotype and UV-induced melanoma formation. Joint segregation results show linkage of a CDKN2-like DNA polymorphism with UV-B-induced melanoma formation in these hybrids. The CDKN2-like polymorphism maps to Xiphophorus linkage group V and exhibits recombination fractions with ES1 and MDH2 allozyme markers consistent with previous localization of the DIFF tumor suppressor locus. Our results indicate that the CDKN2-like sequence we have cloned and mapped is a candidate for the DIFF tumor suppressor gene.

An animal model for human melanoma.

Experimental animal models that are directly relevant to human melanoma are lacking. We propose the Angora goat as a potentially useful field model with experimental potential and to this end have examined the prevalence and site distribution of all skin cancers in 28 Angora goat herds in Queensland, Australia. The prevalence of benign melanocytic lesions (lentigines) and their experimental induction by sunlight were also investigated. Among 1731 goats over 2 years of age, 139 malignant skin tumors were excised from 95 affected animals. The prevalence of squamous cell carcinoma (SCC) was 3.8% and of melanoma, 2.2%. Main site of occurrence of melanoma (83%) was the dorsal surface of the ear; in contrast SCC occurred mostly (84%) on the perineum. Lentigines were darker and more prevalent on the exposed compared with the unexposed surface of the ear in Angoras, analogous to the higher prevalence of nevi on the exposed compared with the less exposed inner surface of the arm in humans. Lentigines, which were also found on the perineum though lighter in color than on the dorsal ear, were absent in young animals under 3 months but were numerous in 1-3 year olds. Furthermore in an experimental substudy eight goats, having one flank repeatedly shorn and the contralateral flank left unshorn, revealed consistently more solar lentigines on the shorn flank (P < 0.05) when both sides were examined after 9 months. Histopathological examination of paired skin biopsies from five of these goats also showed more abundant pigmentation in skin from the exposed, as compared with the unexposed flank. These findings indicate that sunlight induces tumors and lentigines in goats in a highly site-specific manner. The Angora goat model may suggest paradigms for explaining the site differences observed for human melanoma and may also be useful in the future clarification of molecular changes following carcinogenic levels of sun exposure.

Glioblastoma multiforme arising in the irradiated spinal cord of a rhesus monkey (Macaca mulatta).

An adult female rhesus monkey that had received 44.0 Gy of cobalt 60 radiation to 8 cm of the cervical and upper thoracic spinal cord approximately 2.8 years postirradiation developed a sudden onset of self-mutilation and loss of function of the right arm followed progressively by loss of function of the left arm and terminally bilateral paresis of the legs. Histopathologic examination of the cervical spinal cord revealed a glioblastoma multiforme that extended from the cervical medullary junction to the sixth cervical vertebrae. Because of the infrequent occurrence of spontaneous neoplasia in rhesus monkeys and the location in the radiation field, the glioblastoma is believed to be radiation induced.

Radiographically determined growth dynamics of primary lung tumors induced in dogs by inhalation of plutonium.

Beagles were exposed to aerosols of 239PuO2, 238PuO2, or 239Pu(NO3)4. Exponential growth constants for 50 primary lung tumors (23 bronchioloalveolar carcinomas, 22 papillary adenocarcinomas, 5 adenosquamous carcinomas) were calculated in 37 dogs, using sequential thoracic radiography. A wide range in doubling time (6 to 287 days) was observed. Mean +/- SEM doubling time was 93 +/- 10 days for bronchioloalveolar carcinoma, 107 +/- 13 days for papillary adenocarcinoma, and 101 +/- 36 days for adenosquamous carcinoma. Lung tumor growth rate in dogs was comparable to that in human patients with similar histologic tumor types. Linear regression analysis revealed significant (P < or = 0.0001) correlation between doubling time and survival of individual dogs. Doubling time was not significantly dependent on tumor type, sex, age at time of diagnosis, initial lung deposition, or isotope. Extrapolating time to tumor onset from tumor doubling time cannot be used to reliably predict the onset of malignancy.

Solar UV irradiance and some biological consequences: Bombay, India.

Measurements of solar UV radiation (UVR) at Bombay, India, lattitude 18.5 North and longitude 72.5 East were recorded using Eppley UV radiometer for a 2-year period. The UV irradiance is calculated and presented. The annual and diurual trends in the quantitation of UVR are examined. The consequences of solar UVR and its projected increase are discussed with special reference to its biological effects and results of UVR on experimental animal systems vis a vis and epidemiological data in the Indian context.

Ultraviolet radiation-induced skin tumors in a South American opossum (Monodelphis domestica).

A total of 19 male and 21 female South American opossums (Monodelphis domestica) were exposed to 250 J/m2 ultraviolet radiation from FS-40 sunlamps (280-400 nm) three times weekly for 70 weeks. The backs of the opossums were shaved as necessary to remove hair. In order to prevent photoreactivation of ultraviolet radiation-induced pyrimidine dimers by the light-dependent photolyase enzyme of the opossum, ultraviolet radiation-exposed opossums were housed under red lights (600-800 nm). The opossum photolyase requires light in the 320-450 nm range for its activity. Twenty-nine control opossums (14 males and 15 females) were irradiated by fluorescent lights with emission spectra primarily in the visible light range (320-700 nm); these control opossums were also housed under red lights, and their backs were also shaved to remove hair. No skin tumors were observed in control opossums, while ultraviolet radiation-exposed opossums developed a variety of hyperplastic and neoplastic skin lesions on the backs and on a single ear. Hyperplastic lesions included foci of epithelial hyperplasia, dermal fibroplasia, and focal proliferation of dermal melanocytes. A total of 20 ultraviolet radiation-exposed opossums (50%) developed skin tumors, and 13 opossums (32.5%) had more than a single tumor. Epithelial tumors included 25 papillomas, four keratoacanthomas, seven carcinomas in situ, three microinvasive squamous cell carcinomas, two invasive squamous cell carcinomas, and a single basal cell tumor. Ten dermal spindle cell tumors also occurred; most of these appeared to be fibrosarcomas. Two benign melanomas and one malignant melanoma were observed.