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H A Solleveld

Publications and source records attributed to H A Solleveld.

At least 37 records · Page 2Linked to original sources

The gene transfer-misrepair hypothesis of radiation carcinogenesis tested for induction of mammary tumours in rats.

Mammary tumour induction was studied in female WAG/Rij rats following exposure with single doses of 0.3 and 1.2 Gy gamma radiation and with the same total doses delivered in fractions of 2.5 and 10 mGy respectively at intervals of 12 h. All rats were implanted with pellets containing 2 mg of estradiol-17 beta prior to the irradiation. The occurrence of mammary carcinomas and of fibroadenomas was recorded. The relative excess hazard for tumour induction was lower for the fractionated regimens than for the single dose exposures. The results are compatible with the predictions of the gene transfer-misrepair hypothesis for radiation carcinogenesis.

Adenofibroma↗

Spontaneous renal lesions in five rat strains.

A survey of non-neoplastic and neoplastic renal lesions found in 5 rat strains, namely, ACI (August X Copenhagen Irish), A22807 (August), F344 (Fischer), M520 (Marshall), and OM (Osborne-Mendel) is given. The results from this survey indicate that the OM, M520, and ACI rat strains have major disadvantages for their use in long-term toxicology and carcinogenesis studies. Male OM rats had a high incidence of renovascular lesions which consisted of necrotizing arteritis or arteriolitis and intimal thickening of small arteries, and resembled renal lesions described in hypertensive rats and human patients. Predominant renal lesions in the M520 and ACI rat strains included extensive calculus formation at the pyramido-pelvic junction, which was often associated with proliferative pelvic transitional cell lesions and hydronephrosis. The ACI rat strain also had unilateral congenital renal agenesis in about 12% of the animals of either sex. Based on the spectrum of renal lesions observed in the 2 remaining rat strains, namely A28807 and F344, it is difficult to determine which one of the two should be preferred for long-term studies. The A28807 rat strain had less severe chronic renal disease than the F344 but had a higher incidence of pelvic transitional cell hyperplasia. The ultimate choice should be based on the spectrum, incidence, and severity of extra-renal lesions.

Animals↗

Guidelines for combining neoplasms for evaluation of rodent carcinogenesis studies.

In a continuing review of long-term toxicology and carcinogenesis studies in rats and mice, the National Toxicology Program (NTP) is confronted with many problems concerning the interpretation of tumor data. A frequently raised question is: "Should certain neoplasms be combined for overall assessment of rodent carcinogenesis data?" NTP policy is that certain neoplasms may be combined for statistical assessment of tumor data and that hyperplastic responses may be used as supportive evidence. The primary reason for combining neoplastic lesions is to gain more insight into the evidence of the carcinogenicity of a given chemical in that species of animal. This report gives the rationale, criteria, and guidelines used by the NTP for combining neoplasms for the evaluation of long-term rodent toxicology and carcinogenesis studies. The guidelines are based mainly on lesions occurring in the F344/N inbred rat and (C57BL/6 X C3H)F1 mouse and may or may not be appropriate for other strains or species. The concepts of combining neoplasms and sites should be viewed in terms of the study as a whole, since tumor formation is only one of many responses caused by chemicals in mammals. The resulting information becomes part of the "weight of the evidence" for estimating the potential hazard of a given chemical.

Animals↗

Forestomach ulcers in Crj:B6C3 (C57BL/6NCrj x C3H/HeNCrj) F1 mice.

An unusually high incidence of forestomach ulcers was observed in a mouse strain that is used frequently for long-term toxicology studies. Examination of 98 untreated male and 98 untreated female B6C3F1 hybrid mice, the majority of which were between 105 and 113 weeks of age, revealed forestomach ulcers in 52% of the males and 54% of the females. Glandular stomach ulcers were uncommon, being found in only four female mice. The incidence of the ulcers increased with age. The etiology of the lesion is unknown.

Animals↗

Multiple organ carcinogenicity of 1,3-butadiene in B6C3F1 mice after 60 weeks of inhalation exposure.

Groups of 50 male and 50 female B6C3F1 mice were exposed 6 hours per day, 5 days per week, for 60 to 61 weeks to air containing 0, 625, or 1250 parts per million 1,3-butadiene. These concentrations are somewhat below and slightly above the Occupational Safety and Health Administration standard of 1000 parts per million for butadiene. The study was designed for 104-week exposures but had to be ended early due to cancer-related mortality in both sexes at both exposure concentrations. There were early induction and significantly increased incidences of hemangiosarcomas of the heart, malignant lymphomas, alveolar-bronchiolar neoplasms, squamous cell neoplasms of the forestomach in males and females and acinar cell carcinomas of the mammary gland, granulosa cell neoplasms of the ovary, and hepatocellular neoplasms in females. Current workplace standards for exposure to butadiene should be reexamined in view of these findings.

Air Pollutants, Occupational↗

The value and significance of life span and scheduled termination data in long-term toxicity and carcinogenesis studies.

Consideration is given to the age association of lesions, the duration of long-term toxicity and carcinogenesis studies, and to the value and significance of including scheduled termination in such long-term studies. There is now enough evidence that age and cancer are associated. It is argued that the increase in incidence of lesions with age has such disadvantages that extension of the duration of the long-term toxicity and carcinogenicity study beyond 2 years is not warranted in most cases. Incorporation of scheduled termination in long-term studies gives more insight into the biologic behavior of toxic lesions and cancer and may enable one to make a distinction between "incidental" and "fatal" lesions. This distinction may be important for the statistical evaluation of data from chemical carcinogenesis studies.

Aging↗

Biological and clinical consequences of longitudinal studies in rodents: their possibilities and limitations. An overview.

Rats and mice are used in gerontological research primarily because of their relatively short life spans, ease of handling, and the relatively low costs of production and maintenance under controlled environmental conditions of large number of rodents as compared to larger laboratory animal species. They are being used as models for studying intrinsic aging processes, processes that give rise to diseases associated with aging, and the influence of environmental factors on these processes. Contrary to the situation in man, longitudinal studies in rodents can be conducted under well controlled environmental conditions. It has been shown that multiple pathology, the hallmark of aging in man, also occurs in inbred strains of rodents. Some of these lesions are genetically determined and some of them are randomly distributed amongst members of the same inbred strain. Serial killing experiments are necessary to obtain information on the time of development of these lesions in order to interpret properly the outcome of investigations. Furthermore, it has been shown that a considerable variation can exist in the observed maximum ages of the longest-lived animals in cohorts of rats kept under well controlled conditions. For this reason, caution should be exercised in interpreting data from studies which claim maximum lifespan prolongation.

Aging↗

Animals in aging research: requirements, pitfalls and a challenge for the laboratory animal specialist.

The prime goal of aging research is to gain some insight into the basic mechanisms underlying the aging process. The long lifespan and frequent mobility of humans as well as the legal and ethical constraints on human experimentation make man unsuitable for studying the aging process. Therefore animals, particularly rodents, are used in aging research. In studying the aging process in animals, one hopes to find means for the prevention or amelioration of at least some of the disabilities of old age in man. Many intrinsic and extrinsic factors can influence the outcome of animal experiments; hence an extensive monitoring program is a prerequisite in aging research. An important role in controlling the quality of the animals is reserved for the laboratory animal specialist. Since he is faced with all aspects of laboratory animal science, aging research is a challenging area for such a specialist.

Aging↗

Clinicopathologic study of six cases of meningitis and meningoencephalitis in chimpanzees (Pan troglodytes).

Three fatal cases of purulent meningitis and one fatal case of thromboembolic necrotizing meningoencephalitis occurred in chimpanzees from the Primate Center TNO, The Netherlands. In addition, two apes had clinical signs of meningitis and were successfully treated. The severity of the residual hemiparesis and dysphagia in one of these two apes was such that it was killed for humane reasons. The histopathological diagnosis was chronic active meningoencephalitis. Streptococcus pneumoniae was isolated from five apes and Klebsiella pneumoniae from one. In the majority of cases, the primary site of infection was the upper respiratory tract. After reducing the population density, initiating a vaccination program using a commercially available human polyvalent pneumococcal vaccine, and changing the cleaning procedure of the animal facilities, no other cases of meningitis or meningoencephalitis have occurred in the chimpanzee colony in the ensuing 3.5 years.

Animals↗

Natural history of body weight gain, survival, and neoplasia in the F344 rat.

This study involved the fact that knowledge of the natural incidence of neoplastic lesions is essential for interpretation of experiments designed to reveal the effects of potential carcinogens. Although the F344 rat is widely used in chronic (2-yr) testing programs, the natural history of neoplasia after 24 months is not known; thus this study, with 529 male and 529 female inbred F344 rats, was designed to deal with this aspect. This report also included information on growth and longevity. In addition, the tumor rates found in this study were compared with 2-year historic control tumor rates; results revealed the following. 1) Maximum mean body weights were 468 and 330 g for males and females, respectively. Peak weight in males was reached at 77 weeks of age and in females, at 107 weeks of age. 2) There was no clear sex difference in longevity; a median life-span (50% survival age) or 28 months was recorded in both sexes. 3) Variety of neoplastic lesions in animals that were allowed to live out their life-span was not greater than that in animals that were killed between 110 and 116 weeks of age; thus older age was not characterized by unique neoplasms. 4) The incidence of certain neoplasms increased markedly after 110-116 weeks. The data indicated that life-span studies in F344 rats had no advantages over 2-year studies. However, availability of life-span data is essential for interpretation of the 2-year studies.

Age Factors↗

A histopathological survey of aged Praomys (mastomys) natalensis.

This histopathological study shows that Mastomys develops a wide variety of neoplastic and nonneoplastic lesions with age. In comparing neoplastic lesions of Mastomys with those generally found in mice and rats, Mastomys is more or less unique with respect to the development of lymphoepithelial thymomas (40%), parathyroid adenomas (11%), prostatic adenocarcinomas (5%), and gastric carcinoids (4%) and the absence of brain, lung, and mammary tumors. Of the nonneoplastic lesions, prostatic (38%), thymic (12%) and parathyroid (11%) hyperplasia, and moderate to severe generalized degenerative joint disease (96%) occur rarely in mice and rats. Within the limits of this study, in which the age of the animals ranged from 18 to 39 months, a clear-cut age-related pattern was seldom found for most of the lesions occurring in Mastomys.

Aging↗

Absence of anti-acetylcholine receptor antibodies in Praomys (Mastomys) natalensis.

It has been suggested in the past that Praomys (Mastomys) natalensis might be an animal model for human myasthenia gravis. This suggestion was based on the occurrence of thymomas and autoantibody to striated muscle in this animal species. Myasthenia gravis in man is associated with anti-striated muscle antibody and thymoma as well as antiacetylcholine receptor antibody. This prompted us to search for such autoantibodies in Mastomys. There was no evidence of anti-acetylcholine receptor antibody in any of the serum samples tested. The titres found in Mastomys correspond to those observed in human control sera. No difference was found in the number of alpha-bungarotoxin-binding sites at the motor endplate and in muscle extracts between animals with and without thymoma and with and without anti-striated muscle antibody. These findings lead to the conclusion that it is very unlikely that myasthenia gravis occurs with any frequency in Praomys (Mastomys) natalensis.

Acetylcholine↗

Respiratory disease in rats associated with a filamentous bacterium: a preliminary report.

A naturally occurring, chronic disease of the respiratory tract was investigated from the time of its onset to completion of life-time studies in a colony of rats. The disease was characterized by peribronchial lymphoid cuffing, suppurative bronchitis, bronchiectasis and bronchial abscesses. Its onset in the colony occurred a few months after an epizootic of Sendai virus infection. Limited retrospective serological testing indicated that Mycoplasma pulmonis may have been present in the colony at that time and continued to persist throughout life in some rats in the colony. Although of uncertain significance, light and electron microscopy consistently demonstrated many filamentous bacteria between the cilia on respiratory epithelium and free in bronchial exudate in these cases. Attempts to culture this organism on artificial media were unsuccessful.

Animals↗

Types and quality of animals in cancer research.

In addition to studies in man, animal models may serve as important tools in the detection of the etiology, biology and treatment of certain types of human cancers. Various models have become available by performing life span studies on 2 rat strains, viz WAG/Rij, BN/Bi and (WAG x BN) F1 hybrid and on Praomys natalensis. Several of these models are described. A basic prerequisite for these types of studies is the availability of animals of good quality. After a general description of the quality of laboratory animals the desirable health status of animals in cancer research is discussed.

Animals↗