Hyperplasia and Pheochromocytoma, Adrenal Medulla, Rat

Strandberg, John D.

doi:10.1007/978-3-642-60996-1_51

Cited by 8 publications

(9 citation statements)

References 26 publications

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“…Hyperplasia and neoplasia arise frequently in the rat adrenal medulla, either spontaneously in the course of aging or in response to a wide variety of xenobiotic agents (23). The same adrenal lesions are rarely observed in humans and other animal species (24).…”

Section: Introductionmentioning

confidence: 99%

The Association Between Severe Nephropathy and Pheochromocytoma in the Male F344 Rat— The National Toxicology Program Experience

et al. 1999

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The possible correlation between the severity of chronic progressive glomerulonephropathy (CPN) and the incidence of adrenal pheochromocytoma was examined in selected studies of male Fischer 344 (F344) rats at the National Toxicology Program (NTP). The NTP historical control database was first examined in order to determine whether there was association between the severity of CPN and the occurrence of adrenal pheochromocytoma in unexposed animals. Following this analysis, the 125 most recent NTP studies conducted in F344 rats were examined in order to determine how frequently chemicals that cause increased severity of CPN showed an increased incidence of pheochromocytoma. Finally, we examined the association between the incidence of pheochromocytoma and the severity of CPN in those NTP studies with chemically related increased rates of pheochromocytoma. In control male F344 rats surviving beyond 21 mo, the incidence of adrenal pheochromocytoma was consistently higher in animals with more severe CPN. This association was significant ( p < 0.05) both for 900 NTP inhalation study controls and 900 NTP feeding study controls. An association was not consistently observed when dosed groups were considered. Although 22% (28/125) of NTP studies reported a chemically related increased severity of CPN, only 3 of these reported a corresponding significant increase in the incidence of pheochromocytoma. Of 6 NTP studies that reported increased incidence of pheochromocytoma, animals with pheochromocytoma from 5 of those studies had some degree of increased severity of CPN. However, the estimated strength of the correlation with the severity of CPN varied from study to study and was often quite different from that indicated by an analysis of the more extensive NTP control databases. The possible correlation between the severity of CPN and the incidence of pheochromocytoma may influence interpretation of carcinogenic effects observed at this site.

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Section: Introductionmentioning

confidence: 99%

The Association Between Severe Nephropathy and Pheochromocytoma in the Male F344 Rat— The National Toxicology Program Experience

et al. 1999

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“…These lesions, which include diffuse hyperplasia, nodular hyperplasia, and pheochromocytomas, also occur frequently in rat carcinogenicity studies, and their induction appears to reflect exacerbation of proclivities toward their spontaneous development in susceptible rat strains (Tischler and DeLellis, 1988;Strandberg, 1996). The lesions occur most frequently in male rats, with reported lifetime frequencies of over 80% in the Wistar strain and over 30% in the Fisher 344 and Sprague-Dawley strains.…”

Section: Toxicologymentioning

confidence: 99%

“…Substances that induce pheochromocytomas in rats are pharmacologically diverse and, for the most part, nongenotoxic. These have recently been reviewed (Strandberg, 1996). It has been hypothesized that a common denominator in their mode of action is stimulation of chromaffin cell proliferation by neurally derived signals that also regulate catecholamine production and release.…”

Section: Toxicologymentioning

confidence: 99%

Comparative Studies of Chromaffin Cell Proliferation in the Adrenal Medulla of Rats and Mice

et al. 1997

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“…Multiple factors that affect the pathogenesis of pheochromocytoma in rats include genetic background, chronic high levels of growth hormone or prolactin associated with pituitary tumors, dietary factors, and stimulation of the autonomic nervous system (38). In most instances, the exogenous agents that induce adrenal medullary neoplasia do not cause DNA damage; thus, many of these agents may in uence the carcinogenic response of the adrenal medulla through an indirect mechanism (41).…”

Section: Introductionmentioning

confidence: 99%

Association of Adrenal Pheochromocytoma and Lung Pathology in Inhalation Studies with Particulate Compounds in the Male F344 Rat—The National Toxicology Program Experience

Ozaki¹,

Haseman

Hailey³

et al. 2002

Toxicol Pathol

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Systemic hypoxemia , occurring in space-occupyin g lung pathologies such as in ammation and neoplasms, reduces the gas exchange area and stimulates catecholamine secretion from the adrenal medulla where chronic endocrine hyperactivity may lead to hyperplasia and neoplasia. We investigated the possible correlation between nonneoplasti c chronic pulmonary lesions and adrenal pheochromocytom a in 9 recent, NTP, 2-year particulate inhalation studies in male F344 rats. Re-evaluation for chronic active in ammation, interstitial brosis, alveolar epithelial hyperplasia, squamous metaplasia, proteinosis, and histiocytosis revealed signi cant associations of pheochromocytom a only with the severity of in ammation and brosis. Nickel oxide, cobalt sulfate, indium phosphide , talc, and nickel subsul de studies showed chemical-related incidences of adrenal pheochromocytom a and signi cant ( p < 0.01) associations with in ammation and brosis. Gallium arsenide, vanadium pentoxide, molybdenum trioxide, and nickel sulfate hexahydrat e studies revealed an increased incidence and/or severity of nonneoplasti c lung lesions, but no increased incidence of pheochromocytoma . Although gallium arsenide and molybdenum trioxide showed no dose-related increase in pheochromocytoma , a signi cant ( p < 0.01) correlation of the latter with the severity of brosis and in ammation occurred. In the vanadium pentoxide and nickel sulfate hexahydrat e studies, no relationship between nonneoplasti c lung lesions and pheochromocytom a was manifested. Our investigation assessed the strength of these various associations and supports the possible roles of 2 chronic pulmonar y lesions-brosis and in ammation-and hypoxemi a in the induction of pheochromocytom a in the F344 male rat.

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Hyperplasia and Pheochromocytoma, Adrenal Medulla, Rat

Cited by 8 publications

References 26 publications

The Association Between Severe Nephropathy and Pheochromocytoma in the Male F344 Rat— The National Toxicology Program Experience

The Association Between Severe Nephropathy and Pheochromocytoma in the Male F344 Rat— The National Toxicology Program Experience

Comparative Studies of Chromaffin Cell Proliferation in the Adrenal Medulla of Rats and Mice

Association of Adrenal Pheochromocytoma and Lung Pathology in Inhalation Studies with Particulate Compounds in the Male F344 Rat—The National Toxicology Program Experience

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