Frequency of chromosome aberrations induced by trimethyltin chloride in human peripheral blood lymphocytes in vitro: related to age of donors.
TL;DR: Human peripheral blood lymphocytes of healthy male and female individuals of different age groups were treated with two aqueous doses of trimethyltin chloride and Chromatid and chromosome types of aberrations were observed to be increased in both treated sets in all age groups.
Abstract: Human peripheral blood lymphocytes of healthy male and female individuals of different age groups were treated with two aqueous doses (0.5 microgram and 1.0 microgram) of trimethyltin chloride in mitogen stimulated and serum supplemented culture medium for 72 h at 37 degrees C. Chromatid and chromosome types of aberrations were observed to be increased in both treated sets in all age groups. Significant variations were observed between age groups (P less than 0.001) and between experimental sets (P less than 0.001). Moreover, interaction of chemical and donors age was statistically highly significant (P less than 0.05-P less than 0.001). However, no linear correlation between the increase of donor's age and aberrations was observed.
Citations
More filters
[...]
TL;DR: The hypothesis that stable chromosome aberration show a greater accumulation with age than do unstable aberrations is supported and suggested that lifestyle factors contribute to the accumulation of cytogenetic damage.
Abstract: Individual responses to the aging process are variable and are affected by genetic as well as environmental factors. Fluorescent in situ hybridization with whole chromosome probes (‘chromosome painting’) provides an efficient approach for detecting structural chromosome aberrations in human lymphocytes. This rapid and sensitive technique is an effective tool for quantifying chronic exposure to environmental agents which may result in an accumulation of cytogenetic damage with age. We have applied this technology to a normal, putatively unexposed, population to document the relationship between age and the accumulation of cytogenetic damage, as well as to establish a baseline frequency of stable aberrations. Using probes for chromosomes 1, 2 and 4 simultaneously, the equivalent of 1000 metaphases was scored for stable and unstable aberrations from each of 91 subjects ranging in age from newborns (umbilical cord bloods; n = 14) to adults aged 19 to 79 years. Each subject (or one parent of each newborn) completed an extensive questionnaire to identify possible lifestyle factors that may influence the frequency of cytogenetic damage. Our findings show a significant increase in stable aberrations (translocations and insertions) with age (p < 0.0001). We also observed age-related increases with dicentrics (p < 0.0001) and acentric fragments (p < 0.0001). Relative to the frequencies observed in cord bloods, the frequencies of stable aberrations, dicentrics, and acentric fragments in adults aged 50 and over were elevated 10.6-fold, 3.3-fold, and 2.9-fold, respectively. Nine variables other than age are significantly associated with the frequency of stable aberrations; these are: smoking (two variables), consumption of diet drinks and/or diet sweeteners (4 variables), exposure to asbestos or coal products (1 variable each), and having a previous major illness (1 variable). Newborns whose mothers smoked during pregnancy had a 1.5-fold increase in stable aberrations (p = 0.029). Repeat samples from a subset of the adults indicate that for most subjects there is little change in individual translocation frequencies over a period of two to three years. These results support the hypothesis that stable chromosome aberrations show a greater accumulation with age than do unstable aberrations and suggest that lifestyle factors contribute to the accumulation of cytogenetic damage.
275 citations
Journal Article•
[...]
TL;DR: The results point to an age-related increase of the chromosome damage in lymphocytes and emphasize the need to take into account the potential confounding effect of this variable in the design of biomonitoring studies based on chromosome damage.
Abstract: Intra- and interindividual variations of baseline frequencies of cytogenetic end points in lymphocytes of human populations have been reported by various authors. Personal characteristics seem to account for a significant proportion of this variability. Several studies investigating the role of age as a confounding factor in cytogenetic biomonitoring found an age-related increase of micronucleus (MN) frequency, whereas contradictory results were reported for chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). We have quantitatively evaluated the effect of age on SCE, CA, and MN through the analysis of a population sample that included data from several biomonitoring studies performed over the last few decades in 12 Italian laboratories. The large size of the data set, i.e., more than 2000 tests for each end point, allowed us to estimate the independent effect of age, taking into account other covariates, such as sex, smoking habits, occupational exposure, and inter- and intralaboratory variability. A greater frequency of the mean standardized values by increasing of age was observed for all of the end points. A leveling off was evident in the last age classes in the trend of MN frequencies. Frequency ratios (FRs), which express the increase of the cytogenetic damage with respect to the first age classes, i.e., 1-19 years, were estimated using Poisson regression analysis after adjustment for the potential confounding factors and confirmed the increasing trend by age class for all three end points. The most dramatic increase was observed for MN, with a FR that approaches the value of 2 at the age class 50-59 (FR, 1.97; 95% confidence interval, 1.43-2.71) and remains substantially unchanged thereafter. The trend of FRs for CA is more homogeneous, with a constant rise even in the older classes, whereas the frequency of SCE increases with age to a lesser extent, reaching a plateau in the age class 40-49 and the maximum value of FR in the age class over 70 (FR, 1.14; 95% confidence interval, 1.07-1.23). In conclusion, our results point to an age-related increase of the chromosome damage in lymphocytes and emphasize the need to take into account the potential confounding effect of this variable in the design of biomonitoring studies based on chromosome damage.
190 citations
[...]
TL;DR: An overview about the environmental distribution of organometal(loid) compounds and the potential hazardous effects on animal and human health is given.
Abstract: The biochemical modification of the metals and metalloids mercury, tin, arsenic, antimony, bismuth, selenium, and tellurium via formation of volatile metal hydrides and alkylated species (volatile and involatile) performs a fundamental role in determining the environmental processing of these elements. In most instances, the formation of such species increases the environmental mobility of the element, and can result in bioaccumulation in lipophilic environments. While inorganic forms of most of these compounds are well characterized (e.g., arsenic, mercury) and some of them exhibit low toxicity (e.g., tin, bismuth), the more lipid-soluble organometals can be highly toxic. Methylmercury poisoning (e.g., Minamata disease) and tumor development in rats after exposure to dimethylarsinic acid or tributyltin oxide are just some examples. Data on the genotoxicity (and the neurotoxicity) as well as the mechanisms of cellular action of organometal(loid) compounds are, however, scarce. Many studies have shown that the production of such organometal(loid) species is possible and likely whenever anaerobic conditions (at least on a microscale) are combined with available metal(loid)s and methyl donors in the presence of suitable organisms. Such anaerobic conditions can exist within natural environments (e.g., wetlands, pond sediments) as well as within anthropogenic environmental systems (e.g., waste disposal sites and sewage treatments plants). Some methylation can also take place under aerobic conditions. This article gives an overview about the environmental distribution of organometal(loid) compounds and the potential hazardous effects on animal and human health. Genotoxic effects in vivo and in vitro in particular are discussed.
126 citations
Cites background from "Frequency of chromosome aberrations..."
[...]
[...]
TL;DR: This review summarizes current data from in vivo and in vitro studies of the neurotoxic effects of TMT, focusing on the hypotheses regarding the mechanisms leading to neuronal death induced by the toxin.
Abstract: Trimethyltin (TMT), an organotin compound with neurotoxicant effects selectively localised in the limbic system and especially marked in the hippocampus, is considered a useful tool to obtain an experimental model of neurodegeneration. Animals exposed to TMT develop behavioural alterations (hyperactivity and aggression), cognitive impairment (memory loss and learning impairment) and spontaneous seizures. TMT induces selective neuronal death involving the granular neurons of the Fascia Dentata and the pyramidal cells of the Cornu Ammonis, with a different pattern of severity and extension according to the various species studied and the dosage schedule. TMT-induced neurodegenerative events are associated with the activation of astrocytes and microglial cells and with the upregulation of proinflammatory cytokines. While the mechanisms by which TMT induces neurodegeneration are still not understood, many hypotheses seem to suggest that neuronal damage could be largely dependent on calcium overload. This review summarizes current data from in vivo and in vitro studies of the neurotoxic effects of TMT, focusing on the hypotheses regarding the mechanisms leading to neuronal death induced by the toxin.
102 citations
Cites background from "Frequency of chromosome aberrations..."
[...]
References
More filters
[...]
TL;DR: In this paper, the basic theory of analysis of variance by considering several different mathematical models is examined, including fixed-effects models with independent observations of equal variance and other models with different observations of variance.
Abstract: Originally published in 1959, this classic volume has had a major impact on generations of statisticians. Newly issued in the Wiley Classics Series, the book examines the basic theory of analysis of variance by considering several different mathematical models. Part I looks at the theory of fixed-effects models with independent observations of equal variance, while Part II begins to explore the analysis of variance in the case of other models.
5,719 citations
[...]
TL;DR: A total of 174 test agents, including pharmaceuticals, food additives, pesticides and organic extracts of air and water pollutants, was tested for mutagenicity in mice using the modified dominant lethal assay, with results determined by increased early fetal deaths per pregnancy and, in some instances, also indirectly by reduction in total implants per pregnancy.
Abstract: A total of 174 test agents, including pharmaceuticals, food additives, pesticides and organic extracts of air and water pollutants, was tested for mutagenicity in mice using the modified dominant lethal assay. In concurrent control populations, the mean weekly pregnancy rate was 66% and exceeded 30% in 99% of all weeks; the distribution of weekly mean total implants per pregnancy was symmetrical around a peak of 11.5–11.9 and was never less than 8; mean early fetal deaths per pregnancy were
450 citations