/pdf/evolution-at-two-levels-in-humans-and-chimpanzees-4j80qi0jr2.pdf

Evolution at two levels in humans and chimpanzees

A deletion of the Y chromosome at the distal portion of band q11 was found in 6 men with normal male habitus but with azoospermia. Five of them were found during a survey of 1170 subfertile males while the sixth was karyotyped because of slight bone abnormalities. These findings, together with a review of the literature, suggest that on the distal portion of the nonfluorescent segment of the long arm of the Y, factors are located controlling spermatogenesis.

Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm.

There are many possible micronucleus assays involving different test organisms and tissues. Because micronuclei arise from chromosomal fragments or chromosomes that are not incorporated into daughter nuclei at the time of cell division, the assay detects both clastogens and agents that affect the spindle apparatus. We know of no case in which micronuclei and chromosomal breakage (or loss) have been shown to occur independently of one another in any dividing cell population. This relationship is so close that false-positives and false-negatives (insofar as the detection of tissue-specific chromosome damage is concerned) should be determined primarily by the statistics of sampling. The production of micronuclei in various experimental organisms has been reviewed. Although there are several promising experimental approaches such as the use of meiotic plant cells or human cells in culture, only one form of the assay, the in vivo mammalian bone-marrow polychromatic erythrocyte (PCE) assay, has been sufficiently developed to be considered a standard assay. More than 150 chemicals have been tested in this assay, with varying degrees of rigor. The data from the literature have been summarized and evaluated in light of the work Group's recommendations for an adequate test. The standards for an adequate test are an important part of the recommendations. These standards, although based on the most recent information available to us, are subject to change because this assay is still evolving. The most important recommendations in this report are: (1) at least 500 PCE should be examined from each of 8 animals to detect an increase of about 4‰ (per thousand) PCE when the background is less than 4 per 1000, (2) sampling should be extended to at least 72 h after the initial treatment, with sampling intervals no greater than 24 h, and (3) the highest possible doses should be used. The success rate of the assay to detect chemicals designated by the Environmental Protection Agency (EPA) as carcinogens is difficult to estimate for several reasons. First, few chemicals designated as noncarcinogens were studied, although in routine testing noncarcinogens are expected to be much more common than carcinogens. Hence, the rate of false-positives (insofar as the detection of cancer is concerned), which ought to be one of the strongest features of the assays, could not be estimated. Second, few chemicals have been tested as rigorously as this report recommends. Hence, the rate of false-negatives is almost certainly overestimated. (It is, nevertheless, obvious that false-negatives are to be expected for any tissue-specific in vivo assay like the micronucleus assay. For example diethylnitrosamine, which produces chromosomal aberrations, micronuclei, and cancer in the liver, is not detected in the bone-marrow micronucleus assay.) Third, many carcinogens are species-specific and this fact has not been taken into account. Considering these caveats, the uncorrected detection rate of the chemicals designated as carcinogens by EPA is about 50%. We believe that this would have been significantly higher had all tests been performed according to the test criteria. Further improvements in the assay are to be expected and these may lead to improvements in its success rate. Recent developments are discussed.

The induction of micronuclei as a measure of genotoxicity: A report of the U.S. environmental protection agency Gene-Tox program☆

This paper contains a brief survey of 12 patients with a G/G translocation en tandem and it is suggested, that trisomy of the band 21q22 might be pathogenetic in Down's syndrome.

Down's syndrome. The possibility of a pathogenetic segment on chromosome no. 21.

Short-term tests for carcinogens and mutagens

The treatment of mice with repeated injections of BUdR and FUdR allows for the demonstration of differentially stained metaphases from bone marrow after FPG (fluorescence plus Giemsa; Perry and Wolff, 1974) treatment. Thus, it is possible to determine the number of SCE's under in vivo conditions, which appears as a very promising system for mutagenicity testing. We studied the response of this system in comparison to the micronucleus test using six mutagenic agents: triaziquone, cyclophosphamide (CP), dimethylphenyltriazene (PDMT), methylnitronitrosoguandine (MNNG), dimethylnitrosamine (DMNA), and diethylnitrosamine (DENA). With the exception of MNNG and DENA, all these agents induce both, SCE and micronuclei, MNNG and DENA being ineffective in both systems. The most potent SCE-inducing agent was triaziquone, followed by PDMT, CP, and DMNA. The quantitative comparison indicates that SCE are induced at 1/10–1/100 of the concentrations which are required for the detection of micronuclei.

Comparative in vivo mutagenicity testing by SCE and micronucleus induction in mouse bone marrow.

The amount of ribosomal DNA (rDNA) was determined quantitatively by RNA-DNA hybridization in the genomes of a mother and her daughter, both with the karyotype 45,XX,t(15q21q). The saturation values found were 0.030% (mother), 0.023% (daughter), and 0.022% for the husband and father of the daughter. A detailed cytogenetic analysis of the short arms of the acrocentric chromosomes of these probands allowed the biochemical results to be interpreted in terms of the size of the individual set of nucleolus organizing regions (NORs) present in each proband. The correlation existing between the biochemical and the cytogenetic findings shows that the amount of rDNA in the human genome is not primarily a function of the number of acrocentric chromosomes, but depends on the individual combination of variant NORs occurring in the human genome.

Biochemical and cytogenetic studies on the nucleolus organizing regions (NOR) of man. II. A family with the 15/21 translocation.

We analyzed individual acrocentric chromosomes identified by fluorescence markers as to their association behavior and measured the lengths of their secondary constrictions. Significant differences were found to occur not only between the frequencies of association of pairs of acrocentric chromosomes, but also between the individual homologues. The frequency of association is a constant and characteristic property of an individual acrocentric chromosome. Differences between the frequencies of association of pairs of acrocentric chromosomes result from widely differing contributions of their respective homologues.

On the relationship between the frequency of association and the nucleolar constriction of individual acrocentric chromosomes

Es wird uber die klinischen und cytogenetischen Befunde bei 3 nichtverwandten Patienten mit Partialtrisomie 4q berichtet. In 2 Fallen ist die Chromosomen-aberration durch eine balancierte elterliche Translokation entstanden (t(3p+;4q-) und t(4q-;18q+)) wahrend im 3. Fall eine spontane invertierte Insertion von 4q22→q34 in 4q34 angenommen wird.

Uneinheitlicher Phänotyp bei Partialtrisomie 4q

The hybridization kinetics of DNA with labeled (18s+28s)rRNA from HeLa cells was determined in patients with trisomy 21, healthy probands with normal karyotype and in carriers of a t(DqGq) centric fusion. The results are in, accordance with the saturation values obtained earlier for these probands: Three patients with trisomy 21 showed an increased saturation level. In 2 of these patients the excess of rDNA exceeded the expected value considerably. Three of the investigated translocation carriers t(14q21q) showed significantly reduced saturation values, while results of a fourth proband with a dicentric chromosome t(15q21q) were found to be within the range of normal probands. The heterogeneous results were correlated with the cytogenetic characteristics of the acrocentric chromosomes. It is expected that these differences could be explained on the basis of family analysis.

W. Vogel

Papers

Comparative in vivo mutagenicity testing by SCE and micronucleus induction in mouse bone marrow.

Biochemical and cytogenetic studies on the nucleolus organizing regions (NOR) of man. II. A family with the 15/21 translocation.

On the relationship between the frequency of association and the nucleolar constriction of individual acrocentric chromosomes

Uneinheitlicher Phänotyp bei Partialtrisomie 4q

Biochemical and cytogenetic studies on the nucleolus organizing regions (NOR) of man