摘要:

The purpose of this conference of toxicologists, geneticists, and statisticians is to increase understanding of the role of animal genetics in toxicology by discussion of one aspect of this relationship, namely the genetic structures of the laboratory animal populations used in toxicological assays. It is hoped that discussion and comparison of various attributes of inbred, F1hybrid, and outbred laboratory animal populations will result In recommendations concerning the most appropriate genetic population structures to be used to supply test animals for toxicological studies having different objectives and end points.

ISSN:0098-4108    

DOI:10.1080/15287397909529718

出版商:Taylor & Francis Group    

年代:1979

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287397909529717

出版商:Taylor & Francis Group    

年代:1979

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287397909529719

出版商:Taylor & Francis Group    

年代:1979

数据来源: Taylor

摘要:

Animal models for the study of toxicity are chosen more for pragmatic reasons such as life‐span, ease of handling, and economics than because of a comprehensive process of validation. There is also a tendency to seek the answers to nonspecific questions and then to use those answers in situations where they cannot lead to proper judgments. In some cases, such as in carcinogenicity testing, an uneasy compromise exists between the sensitivity of the model and the background noise. There is scope, by increased attention to both the control of environmental factors and the genetics of the animal models, to increase the sensitivity and validity of the systems that are used in toxicology.

ISSN:0098-4108    

DOI:10.1080/15287397909529720

出版商:Taylor & Francis Group    

年代:1979

数据来源: Taylor

摘要:

The difficulty of extrapolating from inbred mouse strains used for the assessment of toxicological responses to the human population that may be exposed to the potentially toxic substance is discussed. Conventional risk estimation procedures assume little heterogeneity among members of the population in their response to a substance. This ignores the inherent genetic diversity present in human populations. Measurement of enzymic variation reveals that humans are more variable genetically than most mammalian species. Common genetic variants abound. Genetic variability within or between inbred strains of mice is much less. Evaluation of toxicological hazards should also consider responses to potentially toxic substances by individuals who carry rare genetic alleles. The effect of these rare variants on viability is currently unknown. The manner in which levels of genetic variability are affected by population structure is also discussed. In contemporary human populations, migration rates are not sufficiently restricted, nor are inbreeding and phenotypic assortative mating rates sufficiently large, to play important roles in limiting genetic diversity. Hidden genetic variability in human populations could be enormous, leading to much wider responsiveness to the toxic effects of environmental chemicals than presently appreciated. There exists a potential threat that drugs or food additives may be judged harmless when tested in animals less genetically diverse than humans, when they may, in fact, have serious toxic effects in. a nontrivial number of humans, because of the great genetic diversity present.

ISSN:0098-4108    

DOI:10.1080/15287397909529721

出版商:Taylor & Francis Group    

年代:1979

数据来源: Taylor

摘要:

The effects of inbreeding on heterozygosity, mean performance, variation within and between lines, and fixation or loss of genes are discussed. Theoretical predictions for degree of pedigree inbreeding and consequences for genes neutral with respect to fitness are outlined first, and then the likely modifications necessary to account for natural selection during inbred line development are considered. For illustration, some results from experiments with laboratory animals are reviewed.

ISSN:0098-4108    

DOI:10.1080/15287397909529722

出版商:Taylor & Francis Group    

年代:1979

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287397909529723

出版商:Taylor & Francis Group    

年代:1979

数据来源: Taylor

摘要:

There is no scientific justification for the use of random‐bred or outbred rodents in toxicological and carcinogenesis testing. The frequent desire for heterozygosity in a test population can best be met by using Flhybrids of inbred progenitor strains.

ISSN:0098-4108    

DOI:10.1080/15287397909529724

出版商:Taylor & Francis Group    

年代:1979

数据来源: Taylor

摘要:

Genetically uniform or isogenic strains (inbred strains and F1hybrids) have a number of properties that make them valuable in toxicity testing, provided the experimental design can be modified to include more than one such strain. Isogenicity and homozygosity lead to great phenotypic uniformity, high long‐term genetic stability, high identifiability, large differences between strains (individuality), and the possibility of setting up daughter colonies genetically identical to the parents. This in turn means that many isogenic strains are internationally distributed, and that considerable background data exist on the characteristics of the common strains.

ISSN:0098-4108    

DOI:10.1080/15287397909529725

出版商:Taylor & Francis Group    

年代:1979

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287397909529726

出版商:Taylor & Francis Group    

年代:1979

数据来源: Taylor