Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male Muta Mice were given a single intraperitoneal dose of either 1/15 M phosphate buffer (pH 6) as the vehicle control, MMS 40 mg/kg, ENU 150 mg/kg or iPMS 200 mg/kg, at a dose volume of 20 ml/kg. Animals from each group were killed 3 or 63 days after dosing, the DNA extracted from whole testes and epididymal spermatozoa and analysed for mutation frequency. In the testes, no increase in mutation frequency was observed, at either timepoint, for the animals treated with either MMS or iPMS. A slight increase in the mutation frequency, above vehicle control values, was seen in the ENU-treated animals with a 3 day expression time. A 4-fold increase was observed in the ENU-treated animals exposed for 63 days. In the epididymal spermatozoa, all of the test chemicals induced increases in mutation frequency, at both timepoints, with the exception of a negative result for MMS after 3 days. ENU induced a 2.5 and iPMS a induced a 4-fold increase above the control mutation frequency after 3 days. For all treatments, the later sampling time of 63 days gave an approximate 2-fold increase above the results of the 3-day timepoint. These increases amounted to a 2, 4.5 and 11-fold increase above control for MMS, ENU and iPMS, respectively. The Muta Mouse positive selection system appears to be sensitive to both the premeiotic germ cell mutagen, ENU and postmeiotic germ cell mutagens, MMS and iPMS.
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PMID:Preliminary results of ethylnitrosourea, isopropyl methanesulphonate and methyl methanesulphonate activity in the testis and epididymal spermatozoa of Muta Mice. 905 72

Transgenic male C57BL/6 lambda/lacI mice were used to assess the mutagenic response in seminiferous tubules and epididymal spermatozoa 3 days after exposure to ethylnitrosourea (ENU), iso-propyl methanesulfonate (iPMS) and methyl methanesulfonate (MMS). No significant mutagenic response was observed in epididymal spermatozoa for all three compounds, as expected 3 days after treatment. However, ENU and iPMS treated samples demonstrated significant mutagenic inductions relative to controls in seminiferous tubules while MMS treated samples did not. The failure of MMS to induce a mutagenic response in lambda/lacI transgenic mice is likely due to a combination of the low dose used, the short expression time after exposure and the reduced sensitivity to large deletion events in transgenic lambda/lacI shuttle vectors. In addition, ex vivo mutations were measured in control samples and iPMS treated samples, where 33% of mutants from control samples and 35% of mutants from iPMS treated samples were mosaic.
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PMID:Evaluation of the transgenic Lambda/LacI mouse model as a short-term predictor of heritable risk. 905 73

Male C57B1/6 lacI transgenic mice were used to evaluate germ cell mutagenesis in vivo as part of a collaborative study. Groups of 10 mice were administered single intraperitoneal doses of ethylnitrosourea (ENU; 150 mg/kg), isopropyl methanesulfonate (IPMS; 200 mg/kg), methyl methanesulfonate (MMS; 40 mg/kg) or vehicle. Epididymal spermatozoa and testes were recovered 3 days later and DNA isolated subsequently from epididymal spermatozoa and seminiferous tubules were analyzed for lacI mutations. The mutant frequency in seminiferous tubules (average +/- SEM) increased significantly compared with untreated controls (7.2 +/- 0.7 x 10(-5) following treatment with ENU (11.7 +/- 0.8 x 10(-5), p = 0.003) or with IPMS (9.6 +/- 0.5 x 10(-5), p = 0.018) but not following treatment with MMS (8.1 +/- 0.8 x 10(-5), p = 0.213). Group mutant frequencies were not determined for epididymal spermatozoa from MMS- or IPMS-treated mice because of poor DNA recoveries. As another indicator of the genotoxicity of these alkylating agents, the frequencies of micronuclei were determined in the peripheral blood 48 h after carcinogen administration in the same transgenic mice. The micronuclei frequencies were elevated significantly (p < 0.05) by each treatment (IPMS: 1.0%; MMS: 0.94%) compared to vehicle controls (0.3%). In a separate experiment, 40 mg/kg ENU was previously found to increase the frequency of micronuclei in peripheral blood of lacI transgenic mice 48 h after treatment (3.2%; Gibson et al., 1995). These results demonstrate that the lacI transgenic mouse male germ cells are sensitive to some, but not all, mutagens under the conditions used in this experiment. Investigation of other experimental designs would offer additional perspective on the usefulness of this transgenic model for routine mutagenicity testing in germ cells.
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PMID:Evaluation of lacI mutation in germ cells and micronuclei in peripheral blood after treatment of male lacI transgenic mice with ethylnitrosourea, isopropylmethane sulfonate or methylmethane sulfonate. 905 80

Transgenic mice are widely used to detect gene mutations in vivo induced by a variety of chemicals. It is known, however, that no mutagenicity of methyl methanesulfonate (MMS) is detected in epididymal sperm in various transgenic mice assays, although MMS induces the dominant lethal and specific locus mutations in male mice. To investigate the issue of whether unrepaired lesions in DNA of mature sperm can be transformed into mutations during replication of the lambda phage in Escherichia coli cells, we developed an E. coli strain YG5152, which is a derivative of strain SCS-8 but is deficient in the genes encoding O (6)-alkylguanine-DNA alkyltransferases. When lambda LIZalpha phages were treated with MMS or N-ethyl-N-nitrosourea (ENU) in vitro and infected to the E. coli strains, the mutant frequencies of lacI were markedly higher in strain YG5152 than in strain SCS-8. When Big Blue(trade mark) mice were treated with MMS (160 mg/kg) or ENU (125 or 250 mg/kg) and the phages rescued from mature sperm were infected to the strains, the mutation frequency (MF) of phages from ENU-treated mice at a dose of 250 mg/kg in strain YG5152 was about two times higher than that in strain SCS-8. However, no increase in the MF was observed in the MMS-treated mice even in strain YG5152. These results suggest that, although strain YG5152 efficiently detects ex vivo mutations caused by mutagenic alkyl adducts formed by MMS in lambda phage DNA, no detectable levels of mutagenic methyl adducts are present in mature sperm of MMS-treated mice. Possible reasons for this lack of mutagenicity of MMS in mature sperm using transgenic mice assays are discussed.
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PMID:Effects of O (6)-alkylguanine-DNA alkyltransferase deficiency in Escherichia coli as the host for the detection of mutations in lacI transgenic mice. 1052 48

This study was conducted to assess whether a 2-week treatment period is as effective as 4-week treatment for detection of drug-induced toxicity on the male rat reproductive organs using methyl methanesulfonate (MMS). A two-week study at dose levels of 20 or 40 mg/kg and a 4-week study with 20 mg/kg were conducted. The results can be summarized as follows. No deaths and no apparent clinical signs were observed. Body weights and food consumption were decreased at 40 mg/kg in the 2-week study along with testis and epididymis weights. In the 4-week study, epididymis weights were decreased at 20 mg/kg. The rats treated with 20 mg/kg in the 4-week study and those treated with 40 mg/kg in the 2-week study showed decrease of germ cells, exfoliation of germ cells, vacuolar degeneration of Sertoli cell and cell debris in epididymal ducts on histopathological observation. MMS impairment of spermatogenesis was confirmed by stage analysis. It was concluded that a treatment period of 2 weeks is sufficient to allow evaluation of toxic effects of MMS on the male reproductive organs.
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PMID:Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 15). Two-week and 4-week administration study of methyl methanesulfonate (MMS). 1134 39