摘要:

AbstractA description and review of methods for performing per‐litter analyses involving extrabinomial proportion response is provided. It is stressed that the litter should be regarded as the appropriate experimental unit for quantitative analysis in studies for teratogenic or heritable mutagenic effects. Attention is directed at statistical identification of possible treatment effects, such as a positive dose response to a chemical stimulus. The methods range from distribution‐free, nonparametric analyses to models involving parametric distributions such as the beta‐binomial density. It is seen that most current methods require computer implementation. When concern is raised over misspecification of assumptions critical to the statistical analysis, it is argued that relatively parameter‐free methods are appropriate for use. These include statistical bootstrapping and rank‐based

ISSN:0270-3211    

DOI:10.1002/tcm.1770110302

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

年代:1991

数据来源: WILEY

摘要:

AbstractFemale mice of the NMRI strain were treated with a high dose (5 μg) or a low dose (10−2μg) of the synthetic estrogen diethylstilbestrol (DES) or estradiol‐17β (E2) 48 and 24 hr, 24 hr, or 12 hr before death on day 3 after birth. Cultures of epithelium from the uterine cervix and uterine horns as well as of kidney cells were set up, and, after a culture period of 3 days, cells were studied for chromosome number and sister chromatid exchanges. Cervical cells from control females had a distinct peak of tetraploid cells, which was depressed after DES treatment but less so after E2treatment. The tetraploid peak was lower in uterine horn epithelium and was less influenced by DES. No indications were obtained for an estrogen‐induced aneuploid cell population in the uterine horn epithelium or cervical epithelium. The incidence of cells with a high number of sister chromatid exchanges (HFCECs) was only about one‐fifth in uterine horn epithelium from control females compared with cervical epithelium from the same females. In the cervical epithelium, DES at both dose levels and E2at the high dose induced an increased and similar incidence of HFCECs (from about 12.5% in controls to about 35%), which was not related to estrogen exposure time. In uterine horn epithelium, the incidence of HFCECs increased from 2.5% in controls to 8.5% after DES treatment. It is postulated that there is a more pronounced genomic plasticity in the cervical epithelium compared with the uterine horn epithelium. The estrogens had no effect on chromosome number or HFCECs in ki

ISSN:0270-3211    

DOI:10.1002/tcm.1770110303

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe objective of this study was to generate a comprehensive data set of chemically induced malformations inDrosophilausing a detailed morphological examination of the entire fly (phase one). These data were analyzed, in blind, with the goal of developing a standardized set of criteria which could be used in a new, rapid, and economicalDrosophilabioassay useful in the preliminary screening for potential developmental toxicants. After 32 chemicals were tested, formalized criteria were developed to form the basis of a newDrosophilabioassay. These criteria were then applied to the data from the same 32 chemicals (phase two). The data from only 18 of these chemicals met all requirements for evaluation, e.g., statistical significance, minimum fly numbers, sufficient challenge concentration administered, etc. In the new bioassay, rather than the detailed and time‐consuming examination of the entire fly for a multitude of morphological defects, only two specific anatomical sites are examined. These sites are the humeral bristle and the wing blade, with focus placed on two structural defects—a bent bristle and a notch in the wing. These defects were the only two external malformations among the multitude of defects observed in flies treated in the first phase with the 32 chemicals which demonstrated the following characteristics: 1) A consistent concentration‐response in flies treated with a variety of developmental toxicants; 2) a lack of response with most presumptive non‐developmental toxicants; and 3) consistently low‐background incidences in control flies. In both phases, developingDrosophilawere exposed to the test agents from the egg through three larval stages by incorporating a range of concentrations of each chemical into the culture medium. Emerging adults were examined for an array of defects as part of a detailed morphological examination in the first phase, including bent bristles and wing notches. In the second phase, only bent bristle and wing notch data were evaluated. The incidences of bent humeral bristles and wing notches from flies exposed to each of the 18 chemicals were compared with those of concurrent controls. Of the 18 chemicals that could be evaluated using the new bioassay, 13 were known developmental toxicants while the remaining 5 were presumptive negative agents. Ten of the 13 mammalian developmental toxicants were correctly identified with this test (false negative rate of 23%). Four of five apparent non‐developmental toxicants were correctly identified for a false positive rate of 20%. The sensitivity of the bioassay was 77% (10 of 13 known developmental toxicants accurately detected); the specificity was 80% (4 of 5 negative compounds accurately detected); and the overall accuracy was 78% (14 of 18 chemicals accurately detected). We believe ths formalizedDrosophilabioassay is an improved version of previous screening tests using intactDrosophila, and that this bioassay shows promise for the screening of chemicals for their potential to induce development

ISSN:0270-3211    

DOI:10.1002/tcm.1770110304

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

年代:1991

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770110301

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

年代:1991

数据来源: WILEY