摘要:

AbstractTeratogenicity of thalidomide was demonstrated in Wistar rats following a single maternal intravenous injection during the embryonic organogenetic period. When compared to day 13 embryonic DNA isolated from untreated control mothers, differences were observed in the mean wet weights of day 13 embryos from rats treated with thalidomide during days 10 or 11 of gestation, and significantly less amounts of embryonic DNA were recovered from mothers similarly treated on days 10 or 12 of their respective gestation periods. Rat embryonic DNA may be separated into two fractions by stepwise elution from benzoylated DEAE‐cellulose (BD‐cellulose) columns with 1.0 M NaCl (SE‐DNA) and 1.8% (w/v) caffeine (CE‐DNA) solutions, respectively. Other studies using bacterial, yeast, and rat liver DNA suggested that the first fraction contains native DNA, whereas the second may exhibit some degree of single‐stranded character. Similar reproducible chromatographic profiles were obtained using a novel “batch method” developed for general application. Rat embryonic DNA was monitored by labelling in vivo with an i.p. injection of [methyl‐3H]‐thymidine (3H‐TdR) during days 5, 6, and 7 of the gestation period. All samples were analysed on day 13 of gestation. A simple increase in percentage of caffeine‐eluted DNA was not detected in thalidomide treated samples; however, diversity of percent (%) CE‐DNA within litter was noted. Briefly, the percent CE‐DNA values for embryos in one litter were ranked and arbitrarily grouped in classes with limits of mean ± 1 SD, mean ± 2 SD, and so on to generate a characteristic profile of percent CE‐DNA distribution. The number of embryos within the range of each SD unit was expressed as a percentage of each litter. A plot of the ranges of percent CE‐DNA versus percentage of each litter was used to illustrate the distribution profile of the particular litter and to be used for comparison between samples from untreated control and thalidomide and/or dimethylformamide (DMF) treated DNA. Treatment of day 12 mothers with thalidomide produced a majority of embryos having percent CE‐DNA values similar to those of untreated controls with the exception of the inclusion of a second population of embryos with much higher percent CE‐DNA values than those of the untreated controls. Similar treatment of day 11 animals produced a majority of embryos still having percent CE‐DNA values similar to those of untreated controls and also having a second group of embryos with a lower percent CE‐DNA values than those of untreated controls. Following thalidomide treatment of mothers on day 10 of gestation, although the majority of embryos had percent CE‐DNA values similar to the lowest extreme value of the untreated control, the second group of embryos had percent CE‐DNA values even lower than those of the similar respective group from 48 hour treated animal. Results from this study suggest that the teratogenic effect of thalidomide may be simply slowing down the development of certain group of cells, which are then out of synchrony with t

ISSN:0270-3211    

DOI:10.1002/tcm.1770100402

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

年代:1990

数据来源: WILEY

摘要:

AbstractHypotonic NaCl solutions and diluted culture medium were tested for induction of sister chromatid exchanges (SCEs) and chromosomal aberrations (CA). Hypotonic treatment conditions were found to induce high frequencies of CA and SCEs. However, an increase in SCEs was observed only in cells that also had CA. Possible lesions and mechanisms leading to SCEs and CA are discussed.

ISSN:0270-3211    

DOI:10.1002/tcm.1770100403

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe relationship between mutagenesis and carcinogenesis was investigated in T × HT crossbred mice using diaplacental application of ethylnitrosourea (ENU) at different stages of embryonal development. Mutagenesis was detected by induction of coat color spots, and the carcinogenic response was investigated in a long‐term follow‐up study of the F1‐generation. The animals were particularly sensitive to induction of tumors at the central nervous system (CNS)‐skull/vertebra interface (30% and 20% in ENU‐treated male and female offspring, respectively, compared with<1% in controls). There was a correlation between the appearance of these tumors and the presence of color spots. This correlation was low but statistically significant in female offspring. Three other types of tumors showed a correlation with the presence of coat color spots. Liver tumors were significantly increased in color spot‐positive females but unchanged in males. Lung tumors were reduced in color spot‐positive males and appeared earlier in color spot‐positive females. There was a lower incidence of lymphoma/leukemia in all spot‐positive mice. The reduction in tumor incidence beyond the spontaneous rate in spot‐positive animals might be caused by a high cytolethal response to ENU in the relevan

ISSN:0270-3211    

DOI:10.1002/tcm.1770100404

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

年代:1990

数据来源: WILEY

摘要:

AbstractEnhanced cytogenetic damage by the homo‐aza‐steroidal ester of p‐bis (2‐chloroethyl)‐aminophenylacetic acid (ASE) was observed when human lymphocytes in vitro or Ehrlich ascites tumor (EAT) cells in vivo were exposed to nontoxic concentrations of 3‐aminobenzamide (3‐AB). 3‐AB at these concentrations was found to enhance synergistically the cytogenetic damage induced in vivo by cyclophosphamide (CP), a metabolically activated chemotherapeutic, or chlorambucil (CBC) in EAT cells. One hour before i.p. injection of 5‐bromodeoxyuridine (BrdUrd) adsorbed to activated charcoal, EAT‐bearing mice treated i.p. with ASE or CP showed a dose‐dependent increase in sister chromatid exchange (SCE) rates and cell division delays. The treatment of human lymphocytes in vitro with ASE led to the depletion of cellular NAD, and addition of 3‐AB, a potent inhibitor of poly(ADP‐ribose)polymerase [P(ADPR)polymerase], to ASE‐treated human lymphocytes prevented the drop of NAD, which remained at approximately control levels. Also, the in vivo treatment of EAT cells with CBC, ASE, or CP led to the depletion of NAD, whereas addition of 3‐AB to CBC‐, ASE‐, or CP‐treated cells prevented the drop of NAD, which remained at nearly control levels. 3‐AB in conjunction with CBC, ASE, or CP increased the survival time of the EAT‐bearing mice and markedly reduced the ascitic volume. Thus cytogenetic damage induced by ASE plus 3‐AB in vitro and by CBC, ASE, or CP plus 3‐AB in vivo correlates well with (1) the prevention of NAD depletion in the presence of 3‐AB in cells treated with the same alkylating agents in vitro or in vivo and (2) the in vivo antitumor effec

ISSN:0270-3211    

DOI:10.1002/tcm.1770100405

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

年代:1990

数据来源: WILEY

摘要:

AbstractQuercetin was examined for the effects on the two‐stage chemical transformation of BALB/3T3 cells. Quercetin showed initiating action to induce transformation in the cells which were treated with quercetin and subsequently with 0.49 μM 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA). Both the proportion of dishes with transformed foci and the average number of foci per dish increased with the concentration of quercetin (15–45 μM). However, initiating treatment with quercetin did not induce transformation without subsequent TPA treatment. Quercetin inhibited the promotion caused by 0.49 μM TPA in the transformation initiated by 1.9 μM 3‐methylcholanthrene (MCA). The inhibitory effect of 30 μM quercetin was 56% in the number of foci per dish. Thus quercetin was found to have initiating effect on the transformation of BALB/3T3 cells, but to restrain

ISSN:0270-3211    

DOI:10.1002/tcm.1770100406

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

年代:1990

数据来源: WILEY

摘要:

AbstractChromosomal aberrations and cell proliferation were analyzed in the chick embryo blood, limb bud, and facial tissues 12 and 24 hours after cyclophosphamide (CP) administration on day 3. The cytogenic findings were compared with teratogenic effects evaluated on incubation day 8. Low dose (0.3 μg) resulting in heart defects exclusively, increased the frequency of aberrant cells with simultaneous depression of cell proliferation in blood only. High dose of CP (6 μg), besides the heart defects, also induced facial clefts and limb malformations, and strong clastogenic effects associated with mitotic inhibition were observed in all tissues investigated. The results support the idea that the consequences of mutagenic action of cyclophosphamide—cell cycle delay and excessive death of cells with unstable aberrations—result in abnormal morphoge

ISSN:0270-3211    

DOI:10.1002/tcm.1770100407

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

年代:1990

数据来源: WILEY

摘要:

AbstractAutomated image analysis was used to measure the colony diameter and estimate the cell number in colonies under conditions for anchorage‐independent growth (AIG). The calculated values for the number of AIG cells in a colony of a diameter ⩾ 60 μm were decidedly different from the actual values obtained by either automated or manual cell counting. Like animal cells that exhibit AIG, these colonies demonstrating anchorage independence can be enumerated reproducibly. However, the assumption is incorrect that the number of cells (N) in a colony expressing AIG varies directly with a change in the diameter of a colony (d). Whether one counts the number of cells manually in a colony of a definite diameter or arbitrarily uses a diameter function of ⩾ 60 μm as a linear distance that indicates the presence of 50 or more cells in a colony, each procedure has its own built‐in bias. In procedures that require quantitative data, the most reliable procedure is to standardize the values for diameter of colonies with cell numbers in

ISSN:0270-3211    

DOI:10.1002/tcm.1770100408

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.1770100409

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.1770100401

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

年代:1990

数据来源: WILEY