摘要:

AbstractEDB significantly depressed GSH in caput and cauda epididymis, but not in testis, 2 hours following injection. This depression was dose‐related. EDB enhanced EMS‐induced dominant lethal mutations at mating weeks 2 and 3 (of 6). At mating week 2 the fetal death rate was increased two‐fold, while at week 3, the fetal death rate had increased to nearly three‐fold greater than the EMS‐only controls. Enhancement of fetal death rate was confined to postimplantation loss. As with EMS alone, the EDB potentiation of EMS‐induced mutations was limited to postmeiotic stages of spermatogenesis. EDB also enhanced alkylation of rat spermatozoa by labeled EMS. Depression of GSH in reproductive tissues is correlated with a potentiation of dominant lethal mutations, as well as an increase in the binding of EMS to

ISSN:0270-3211    

DOI:10.1002/tcm.1770100602

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractDNA repair and replication after in vitro UV irradiation were determined in cultured peripheral blood lymphocytes from 6 patients with nevoid basal cell carcinoma syndrome (NBCCS) and from a group of control donors. DNA repair synthesis (UDS) was measured in unstimulated lymphocytes by incubation with3H‐TdR in the presence of hydroxyurea for 3 and 6 h after UV irradiation (6‐‐48 J/m2). DNA replication was measured in PHA‐stimulated lymphocytes, UV‐irradiated or mock‐irradiated, by incubation with3H‐TdR for 24 h. The effect of the mitogen was followed during 5 days after stimulation by determining the incorporation of3H‐TdR, the increase of cell number, and the mitotic index. NBCCS and control lymphocytes showed equal sensitivity to UV light in terms of UDS and reduced response to PHA. On the contrary, the mitotic index and the number of cells in stimulated cultures were significantly lower in the affected subjects. These data suggest an altered progression along the cell cycle, which could be characteristic of stimulated NB

ISSN:0270-3211    

DOI:10.1002/tcm.1770100603

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractPrevious studies indicate that gentian violet (GV), a triphenylmethane dye used in agriculture and human medicine, is a clastogen in vitro and a carcinogen in chronically exposed mice and rats. Data on its genotoxic activity, however, have been incomplete and partly contradictory. Mutagenesis and DNA damage experiments were conducted to re‐evaluate the genotoxic potential of GV in both bacterial and mammalian cell systems. GV was mutagenic inSalmonella typhimuriumtester strains TA97 and TA104, but there was little mutagenic activity detected in strains TA98 and TA100. A rat liver homogenate fraction (S9) tended to increase mutagenicity. The major microsomal metabolites of GV, pentamethylpararosaniline and N,N,N′,N′‐tetramethylpararosaniline were less mutagenic in TA97 and TA104, while N,N,N′,N"‐tetramethylpararosaniline was a weak mutagen inSalmonella. GV was not mutagenic in Chinese hamster ovary (CHO) cell strain CHO‐K1‐BH4, and was a questionable mutagen in CHO‐AS52 cells. While GV produced DNA damage as measured by sedimentation of nucleoids derived from B6C3F1mouse lymphocytes treated in vitro, no damage was found in lymphocytes isolated from mice dosed with GV. GV was also a weak producer of gene amplification in an SV40‐transformed Chinese hamster cell line. The results indicate that GV is a point mutagen in bacteria; however, since similar exposure conditions produced weak mutagenic activity in mammalian cells, GV may be carcinogenic by virtue of its c

ISSN:0270-3211    

DOI:10.1002/tcm.1770100604

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractThe developmental toxicity of isoniazid (INH) and the metabolites acetylhydrazide (AH) and isonicotinic acid (INA) were examined with the frog embryo teratogenesis assay‐Xenopus(FETAX). LateXenopus laevisblastulae were exposed to INH, AH, and INA for 96 h in two separate static‐renewal tests with and without the presence of three differently induced metabolic activation systems (MAS). The MAS consisted of uninduced, Aroclor 1254‐induced, and INH‐induced rat liver microsomes. Addition of the INH‐induced MAS decreased the 96 h LC50of INH and AH approximately 1.6‐fold and 7.9‐fold, respectively. The 96 h EC50(malformation) of INH was virtually unaffected; however, the INH‐MAS decreased the teratogenic index (TI) [96 h LC50/96 h EC50(malformation)] nearly 1.8‐fold. The 96 h EC50(malformation) of AH increased approximately 2.0‐fold, decreasing the teratogenic index value 15.8‐fold. INA yielded a teratogenic index value of 2.5. Neither the uninduced MAS nor the Aroclor 1254‐induced MAS had an effect on any of the compounds tested and none of the MAS affected the developmental toxicity of INA. Results from this study suggest that mixed functional oxidase metabolism may alter the developmental toxicity of INH in vitro by producing a more embryolethal, but less teratogenic metabolite(s) than INH or AH themselves. Results are indicative of the utility and versatility of FETAX in evaluating toxicological mechanisms of

ISSN:0270-3211    

DOI:10.1002/tcm.1770100605

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractBacterial ancestry of mitochondria and plastids is now generally accepted. Both organelles contain their own DNA and transcription‐translation apparatus of a prokaryotic type. Due to this fact these systems carry bacteria‐like properties. Thus organellar DNA and ribosomes are essentially different from nuclear DNA and cytoplasmic ribosomes in physical as well as in functional respects. Due to the bacterial character of both types of organelles they are susceptible to various antibacterial chemicals. Inhibitors of bacterial protein synthesis inhibit mitochondrial (plastidial) biogenesis. Therefore the cellular content of mitochondria (plastids)‐made proteins decreases during cytoplasmic turnover or cell division in the presence of these drugs. Such drug activity consequently leads to a reduced capacity for oxidative phosphorylation or photosynthesis. Organellar genomes are less stable and more sensitive to mutagenesis as compared to nuclear genome. It means also that genotoxic agents induce various disorders of mitochondrial (plastidial) functions. Impairments in the respiratory chain are associated with structural as well as functional abnormalities of mitochondria. These are clinically expressed mostly in tissues with a high demand for ATP: brain, heart, skeletal muscle, and retina. On the other hand, some antibacterial inhibitors of mitochondrial biogenesis (e.g., tetracyclines) inhibit selectively tumor cell proliferation. Therefore they may be considered for use in anticancer therapy.The article summarizes the response of mitochondria and plastids in various organisms to drugs and environmental xenobiotics. Various model organisms suitable for detection of xenobiotic effect on mitochondria (plastids) are presented as well as the possible consequences of such intera

ISSN:0270-3211    

DOI:10.1002/tcm.1770100606

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770100601

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY