摘要:

AbstractUsing the cytokinesis‐block technique, lymphocytes from healthy volunteers (n = 9) were evaluated for (1) the radiation dose‐response curve for micronuclei (MN) expression; (2) technique variables on the yield of MN; and (3) the shortest lymphocyte incubation time required for the MN assay. We found that the best fitting of relationships between increasing MN production and increasing irradiation dose (0–4.0 Gy) was the linear‐quadratic model as expressed by the yield equation Y = C + αD + βD2(P= 0.0003). When lymphocytes were irradiated in vitro with 2.0 Gy and harvested at various time intervals, MN increased during the entire 84 hr culture time. The radiation caused a division delay in lymphocyte as indicated by an increased frequency of mononucleated cells and a decreased number of mitotic indices. The data showed that a shortened culture time (60 hr) for the MN assay is possible and that binucleated cells with ⩾ 3 MN were found only in cells irradiated at ⩾ 2.0 Gy. These findings suggest that scoring of MN in lymphocytes may be a practical biological dosimeter for the rapid screening of accidental radiation exposure victims, especially when their clinical manifestations are not obvious. © 1994 W

ISSN:0270-3211    

DOI:10.1002/tcm.1770140102

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe aim of this study was to define the long‐term stability of metabolizing enzymes in activating preparations for short‐term genotoxicity bioassays under various storage conditions. Expressions of cytochrome P450 content, NADPH‐cytochrome (P450) c‐re‐ductase activity, and of the several monooxygenases, such as aminopyrine N‐demethylase (class IIIA P450), p‐nitroanisole O‐demethylase (mixed), dinemorphan N‐demethylase (HB1), ethoxyresorufin O‐deethylase (IA1), ethoxycoumarin O‐deethylase (mixed), and pentoxyresorufin O‐dealkylase (IIB1), were examined in S9 fractions derived from Na‐phenobarbital (PB) plus β‐naphthoflavone (β‐NF) induced male and female mice, stored at −80°C, or lyophilized and stored at −20°C. Lipid peroxidation was also determined. Cytochrome P450 and the associated activities were decreased by 30–82% within 9 months of storage. The pattern and degree of relative stabilities were different for the various isoforms. The IA 1‐like activity, for example, was much more stable (˜49%loss) than IIB 1‐like activities (up to 82% loss). In general, lyophilized enzymes were less stable than directly frozen preparations. In addition, immediately after freeze‐drying (lyophilization), a marked decrease in activity of up to 35% was observed. On the contrary, demethylation of aminopyrine and p‐nitroanisole remains almost constant over 6 months storage at −196°C. The results obtained indicate that either fresh, daily made S9 fractions or, alternatively, fractions stored in liquid nitrogen (up to 6 months) are recommen

ISSN:0270-3211    

DOI:10.1002/tcm.1770140103

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

年代:1994

数据来源: WILEY

摘要:

AbstractTaxol, an inhibitor of microtubule disassembly, is currently under investigation in the therapy of several human cancers. The current investigation was undertaken to characterize potential taxol developmental toxicity in chicks. On one of days 1–4 of incubation, taxol was administered in dimethylsulfoxide (DMSO) or olive oil in a range of doses, the highest of which produced a high incidence of early embryo death. Production of gross structural malformations was sporadic and occurred in vehicle‐treated as well as taxol‐treated embryos. A more common manifestation of taxol toxicity was a syndrome of visceral abnormalities, including regression of the vitelline circulation, dilatation of the atria, and hemorrhage in the left side of the head and thorax, often with decreased eye pigmentation. Regardless of the day of treatment, this syndrome occurred at 4.5–5 days. To investigate the possibility that taxol induced its effect through disruption of angiogenesis in the vitelline circulation, filters soaked in taxol were applied to the margin of the germ disc. No inhibition of vessel development was demonstrated. We conclude that taxol decreases the viability of embryos and that this impairment of survival precludes the development of birth defects. Solvent toxicity is an important confounder in the investigation of taxol embryotoxicity. © 1994 Wiley

ISSN:0270-3211    

DOI:10.1002/tcm.1770140104

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe pyrethroid insecticide permethrin was tested for its ability to induce structural chromosome aberrations (CA) in human lymphocyte cultures and CHO cells, in order to confirm the clastogenic effect of itself and to compare the response of the two different cell types. Permethrin was tested in the range of 50–200 μg/ml in human lymphocyte cultures and in the range of 20–100 μg/ml in CHO cells. In both lymphocyte and CHO cultures, assays were performed in the absence and in the presence of a rat liver activation system (S9 mix). In the absence of S9 mix, two experiments with different duration of the treatment were carried out. Permethrin induced CA in both cultures when it was evaluated in the absence of a metabolic activation system. The activity of a given concentration of permethrin seemed to be decreased more by the reduction of the time of exposure than by the presence of S9 mix. Aberrations induced by permethrin were mainly chromosome‐type aberrations in both cultures. Thus, permethrin can be characterised as an S‐phase independent clastogenic agent. The response of both lymphocyte and CHO cultures was similar, indicating that both systems showed the same sensitivity for detecting the clastogenicity in vitro of permethrin. © 1994 Wiley

ISSN:0270-3211    

DOI:10.1002/tcm.1770140105

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

年代:1994

数据来源: WILEY

摘要:

AbstractEtoposide (VP‐16) is used as an antineoplastic drug in humans. It inhibits topoisomerase II (topo II) activity by forming a ternary complex (DNA‐etoposide‐topo II). This complex prevents the DNA‐strand rejoining activity of topo II, which results in DNA‐strand breaks and the formation of structural chromosome aberrations. Topo II activity is also required for removing regions of DNA catenation prior to chromosome segregation. The possibility exists that patients undergoing etoposide chemotherapy may incur genetic damage and, consequently, may be at a greater risk for developing secondary tumors and having genetically abnormal offspring. We studied the ability of etoposide for inducing both structural chromosome aberrations and aneuploidy in mouse oocytes. Different dosages of etoposide were given to female mice at various times before and after human choronic gonadotrophin injection, and ovulated oocytes were collected 17 h later. The proportions of chromatid acentric fragments and of hyperploid metaphase II oocytes were significantly higher (P<0.01) in the etoposide groups than in concurrent controls. These results indicate that both structural and numerical aberrations can be induced without direct interaction with DNA or with the various organelles associated with chromosome segregation. Additionally, unlike other compounds (vinblastine, colchicine, benomyl, and griseofulvin) that induce both meiotic delay (ovulated metaphase I oocytes and polyploidy) and aneuploidy, etoposide did not cause meiotic delay in oocyte maturation. © 1994 Wiley

ISSN:0270-3211    

DOI:10.1002/tcm.1770140106

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

年代:1994

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770140101

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

年代:1994

数据来源: WILEY