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Reproductive cytotoxicity is predicted by magnetic resonance microscopy and confirmed by ubiquitin-proteasome immunohistochemistry in a theophylline-induced model of rat testicular and epididymal toxicity.

Authors
Tengowski-MW; Sutovsky-P; Hedlund-LW; Guyot-DJ; Burkhardt-JE; Thompson-WE; Sutovsky-M; Johnson-GA
Source
Microsc Microanal 2005 Aug; 11(4):300-312
NIOSHTIC No.
20028998
Abstract
This study investigated the testicular changes in the rat induced by the nonspecific phosphodiesterase inhibitor, theophylline using magnetic resonance microscopy (MRM) and ubiquitin immunostaining techniques. In vivo T1- and T2-weighted images were acquired at 2 T under anesthesia. Increased signal observed in the theophylline-treated rats suggests that leakage of MRM contrast was occurring. In vivo MRM results indicate that day 16 testis displayed an increased T1-weighted water signal in the area of the seminiferous tubule that decreased by day 32. These findings were validated by histopathology, suggesting that in vivo MRM has the sensitivity to predict changes in testis and epididymal tissues. The participation of the ubiquitin system was investigated, using probes for various markers of the ubiquitin-proteasome pathway. MRM can be used to detect subtle changes in the vascular perfusion of organ systems, and the up-regulation/mobilization of ubiquitin-proteasome pathway may be one of the mechanisms used in theophylline-treated epididymis to remove damaged cells before storage in the cauda epididymis. The combined use of in vivo MRM and subsequent tissue or seminal analysis for the presence of ubiquitin in longitudinal studies may become an important biomarker for assessing testis toxicities drug studies.
Keywords
Cytotoxicity; Cytotoxins; Cytotoxic-effects; Toxins; Toxic-effects; Laboratory-animals; Animals; Animal-studies; Microscopy; In-vivo-studies; Histopathology
CODEN
MIMIF7
Publication Date
20050801
Document Type
Journal Article
Email Address
mark_w_tengowski@groton.pfizer.com
Funding Amount
235845
Funding Type
Grant
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R21-OH-007324
Issue of Publication
4
ISSN
1431-9276
Source Name
Microscopy and Microanalysis
State
MO; CT
Performing Organization
University of Missouri, Columbia, Missouri
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