A comparison of male rat and human urinary proteins: Implications for human resistance to hyaline droplet nephropathy

Olson, Michael A.; Johnson, Jolene; Reidy, Charles

doi:10.1016/0041-008x(90)90047-x

Cited by 65 publications

(22 citation statements)

References 23 publications

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“…At pH 5, the proportion of cationic proteins in rat urine (including α 2µ -globulin) was 26%, in human urine (including urinary proteins coded for by a gene of the family which codes for α 2µ -globulin in the rat, e.g., α 1 -microglobulin) only about 4% of the total protein level. This situation seems to make it clear that 1,4-dichlorobenzene exposure is not associated with an increased tumour risk for man [116]. This claim is also supported by the fact that to date no cases of nephrotoxicity have been described in persons handling 1,4-dichlorobenzene.…”

Section: α 2µ -Globulin Nephropathy In Male Rats Treated With 14-dicsupporting

confidence: 66%

1,4‐Dichlorobenzene [MAK Value Documentation, 1992]

2012

The MAK‐Collection for Occupational Health and Safety

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Published in the series Occupational Toxicants , Vol. 4 (1992) The article contains sections titled: Toxic Effects and Modes of Action Pharmacokinetics Effects in Man Effects on Animals Acute toxicity Subacute and subchronic toxicity Reproductive and Developmental Toxicity Genotoxicity and DNA‐Binding Carcinogenicity α 2µ ‐Globulin nephropathy in male rats treated with 1,4‐dichlorobenzene Other Effects Manifesto (MAK value, classification)

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Section: α 2µ -Globulin Nephropathy In Male Rats Treated With 14-dicsupporting

confidence: 66%

1,4‐Dichlorobenzene [MAK Value Documentation, 1992]

2012

The MAK‐Collection for Occupational Health and Safety

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“…This line of reasoning leads supporters ofthe hypothesis to conclude that the acute and chronic renal effects induced in male rats by these chemicals will be unlikely to occur in any species not producing c2u-g, or a very closely related protein, in the large quantities typically seen in the male rat (21)(22)(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

“…Normal human urine, such as that of the female rat, contains relatively little protein, only 1% ofthe total concentration present in mature male rat urine (24 In contrast to 1,4-DCB, which is a CIGA, the closely related isomer 1,2-dichlorobenzene (1,2-DCB) does not induce hyaline droplets and appears to bind covalently to proteins in the male rat liver, plasma, and kidney (102). When (106).…”

Section: Sex and Species Comparison Of Urinary Protein Content Relatementioning

confidence: 99%

“…The multistage concept of carcinogenesis, involving in its simplest form an irreversible initiation phase followed by a stage oftumor promotion (186) 24 weeks of exposure to unleaded gasoline or TMP preceded the 2-week period of EHEN administration. All animals were killed at 65-67 weeks after the commencement of the experiment.…”

Section: Initiation-promotion Studiesmentioning

confidence: 99%

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Hazard evaluation of chemicals that cause accumulation of alpha 2u-globulin, hyaline droplet nephropathy, and tubule neoplasia in the kidneys of male rats.

Hard

Rodgers

Baetcke

et al. 1993

Environ Health Perspect

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This review paper examines the relationship between chemicals inducing ewessive accumulation of a2u-globulin (ai21g) (CIGA) in hyline droplets inmale rat kidneys and the subsequent development of nephoit and rnal tubule nopaia in the male rt. This dose-responsive hyaline droplet accumulation distinguishes CIGA carcinogens fromclssical renal carcinogens. CIGA carcinogens also do not appear to react with DNA and are generally negative in short-term tests for genotoxicity. CIGA or their metabolites bind specifically, but reversibly, tomale rat a2,-g The resulting complex appears to be more resistant to hydrolytic degradation in the proximaltubule than native, unbound a2,-g Singlecell necrosis of the tubule epithelium, with associated granular cast formation and papillary mineralization, is followed by sustained regenerative tubule cell prolifertin, foci oftubulehyerl a inthe aovoited pronal bules, and renal tubule tumor Although stnrcturally similar proteins have been detected in other species, including hu_ms, renal lesios characteristic Of a2,-g nephropathy have not been observed. Epidemiologic investigation has not specifically examined the CIGA hypothesis for humans. Based on cancer bioassays, hormone manipulation studies, investigations in an ae,-g-deficient strain of rat, and other laboratory data, an increased proliferative response caused by chemically induced cytotoxicity appears to play a role in the development ofrenal tubule tumors in male rats Thus, it is reasonable to suggest that the renal effects induced in male rats by chemicals causing a2.-g accumulation are unlikely to occur in humans. IntroductionFor most hazardous chemicals, adequate human data are not available, and risk analyses must rely on information from laboratory studies of rats or mice. The inference that the results ofanimal experiments can be applied to humans is a fundamental principle of all toxicologic research. This analysis deals with a specific case, however, where the male rat seems to respond in a manner different from other laboratory species. The possibility of a unique response in the rat among laboratory animals raises questions about the applicability of the rat data to other species, including humans. Our review evaluates the matter of human 'Medical Research Council relevance and describes the types of information needed for hazard assessment of such chemicals.A variety of organic chemicals have produced specific renal lesions in male rats in the form of a protein (hyaline) droplet nephropathy accompanied by accumulation of a2%-globulin (a2.-g) [reviewed in (1,2)]. Among the chemicals tested are paraffins (3,4), decalin (decahydronaphthalene) (5,6), petroleum-based and synthetic fuels (7), military aviation propellants (8), and 2,2,4-trimethylpentane (TMP) (9). As seen in Table 1, which lists a sampling ofchemicals that have been tested, many are of considerable regulatory and commercial interest. For example, isophorone is a chemical intermediate of major industrial importance. Aviation and automotive fuels fit i...

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“…As to the sex difference, male rodents are frequently affected to a greater extent than females. Several factors including potential hormonal effects and total amounts of specific types of urinary proteins have been suggested for this difference [25,27,29,30,31].…”

Section: Factors Affecting Calculus Formationmentioning

confidence: 99%