Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00249 (Mutagen)
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The criteria for reproductive test selection which were set forth in the beginning of this chapter required that the tests be objective, technically sound, biologically stable, sensitive and feasible. All of the tests which have been discussed can generate objective quantitative data (Table 1). Testicular tonometry appears to be a technically sound procedure which measures a biologically stable parameter, although this remains to be proven. Sperm counts are definitely not a biologically stable parameter. There is insufficient information to judge the biological stability of data obtained from sperm cervical mucus interaction. Data from a number of laboratories suggest that the zona-free hamster egg assay gives stable results when repeated with the same donor, and the tests as performed in specialized laboratories are technically sound at the present time. However, the number of laboratories which can perform the assay is limited. Sensitivity to early toxicity is a very important criterion for test selection. Physical examination does not meet this criterion, endocrine studies do not, and sperm counts do not. Not enough information is currently available to determine the sensitivity of sperm motility assessment. Sperm morphology assessment may be the most sensitive early indicator of reproductive toxicity which is currently available. There is a large body of clinical and basic science literature which suggests that sperm morphology may reflect acute stress effects on the testes. The feasibility of these tests vary. Sperm motility may be feasible only in longitudinal studies in which the video equipment can be set up in a laboratory which is doing repeated assessments. Sperm morphology assessment does not require any specialized equipment in the field. Studies of sperm cervical mucus interaction, for the reasons already stated, remain non-feasible at this time. Tests of sperm-egg interaction are probably feasible if spermatozoa can be shipped to a specialized laboratory for assessment. Thus, there are now a number of new tests for male reproductive function which are available, and which are practical. It is time for this technology to be transferred from the basic science laboratory for application in human reproductive risk assessment.
Teratog Carcinog Mutagen 1984
PMID:Laboratory tests for human male reproductive risk assessment. 614 22

Neuronal genotoxic insults from oxidative stress constitute a putative molecular link between stress and depression on the one hand, and cognitive dysfunction and dementia risk on the other. Oxidative modifications to DNA are repaired by specific enzymes; a process that plays a critical role for maintaining genomic integrity. The aim of the present study was to characterize the pattern of cerebral DNA repair enzyme regulation after stress through the quantification of a targeted range of gene products involved in different types of DNA repair. 72 male Sprague-Dawley rats were subjected to either restraint stress (6 h/day) or daily handling (controls), and sacrificed after 1, 7 or 21 stress sessions. The mRNA expression of seven genes (Ogg1, Ape1, Ung1, Neil1, Xrcc1, Ercc1, Nudt1) involved in the repair of oxidatively damaged DNA was determined by quantitative real time polymerase chain reaction in the prefrontal cortex (PFC) and hippocampus (HC). DNA repair gene expression in PFC exhibited a general trend towards an induction after acute stress and a decrease after subchronic exposure compared to control animals. After chronic stress, a normalization towards control levels was observed. A similar pattern was seen in HC, but with overall smaller effects and without the induction after acute stress. Nuclear DNA damage from oxidation as measured by the comet assay was unaffected by stress in both regions. We conclude that psychological stress have a dynamic influence on brain DNA repair gene expression; however, since we were unable to identify concurrent changes in DNA damage from oxidation, the down-stream consequences of this regulation, if any, remains unclear.
Mutat Res Genet Toxicol Environ Mutagen 2015 Jan 15
PMID:Dynamic regulation of cerebral DNA repair genes by psychological stress. 2572 46