Sister chromatid exchanges in lymphocytes of normal and alcoholic subjects

The effects of alcohol consumption, cigarette smoking and age on sister chromatid exchangen (SCE) frequency in human lymphocytes were assessed by means of multiple linear regression. An increase in SCE rates was associated with alcohol consumption (p=0.0001), smoking (p=0.0231), and, to a small extent (p=0.057), age. These three confounding factors explain 48% of the inter-personal variation in SCE rates among subjects studied.We are grateful to Dr D. Krapavickaité for performing, the statistical analysis, and to Mrs V. Navickiené for technical assistance. We also wish to thank Dr B. Lambert (Stockholm, Sweden) for his valuable suggestions.     

Genotype-specific reduction in methyl nitrosourea (MNU) induced sister chromatid exchanges (SCE) in vivo during aging

We studied mice from five strains (BALB/c, C3H/HeSnJ, C57BL/6J, Csb and 129/ReJ) at two ages (young, 10 +/- 1 weeks; and old, 67 +/- 3 weeks) for the induction of sister chromatid exchanges (SCEs) in vivo by methyl nitrosourea (MNU). The SCE frequency is genotype-specific. The F1 phenotype resembles the 'low' responding parent. SCE induction is significantly lower in the older animals of each strain than their younger counterparts, and the reduction of SCE/cell with old age is strain-specific. A general explanation for these results must include strain differences in relative mutagenic sensitivity, genotype-specific pattern of reduction in DNA repair and other such factors affecting SCE formation, with old age.     

Steroid hormones enhanced sister-chromatid exchange in cultured CHO cells

The influence of steroid hormones on the induction of sister-chromatid exchange (SCE) in cultured CHO cells was studied. It was observed that estradiol-17 beta, estriol, estrone and ethynyl estradiol treatments enhanced SCE rates compared to the controls. Overall, these compounds produced a dose response effect. The importance of a detailed study on the long-term genetic effects of steroids on mammalian cells is emphasized.     

Steroid hormones enhanced sister-chromatid exchange in cultured CHO cells

Summary The influence of steroid hormones on the induction of sister-chromatid exchange (SCE) in cultured CHO cells was studied. It was observed that estradiol-17 , estriol, estrone and ethynyl estradiol treatments enhanced SCE rates compared to the controls. Overall, these compounds produced a dose response effect. The importance of a detailed study on the long-term genetic effects of steroids on mammalian cells is emphasized.This work was supported by NIH-Minority Biomedical Research Support Program (MBRS), Grant No. RR 08124-11. The author is thankful for the technical assistance provided by NIH-MBRS student, Hoang Duong.     

Genotype-specific reduction in methyl nitrosourea (MNU) induced sister chromatid exchanges (SCE) in vivo during aging

Summary We studied mice from five strains (BALB/c, C3H/HeSnJ, C57BL/6J, Cs^b and 129/ReJ) at two ages (young, 10±1 weeks; and old, 67±3 weeks) for the induction of sister chromatid exchanges (SCEs) in vivo by methyl nitrosourea (MNU). The SCE frequency is genotype-specific. The F₁ phenotype resembles the low responding parent. SCE induction is significantly lower in the older animals of each strain than their younger counterparts, and the reduction of SCE/cell with old age is strain-specific. A general explanation for these results must include strain differences in relative mutagenic sensitivity, genotype-specific pattern of reduction in DNA repair and other such factors affecting SCE formation, with old age.     

The alcohol syndromes: the intrarecombigenic effect of acetaldehyde

Sister chromatid exchange was studied in lymphocyte and fibroblast cultures. Alcohol caused no disturbance under normal conditions but an acetaldehyde level above 40 muM inhibited cell multiplication and elevated SCE considerably. A high acetaldehyde level is thought to elicit the fetal alcohol syndrome, a view supported by clinical and experimental observations.     

The alcohol syndromes: The intrarecombigenic effect of acetaldehyde

Summary Sister chromatid exchange was studied in lymphocyte and fibroblast cultures. Alcohol caused no disturbance under normal conditions but an acetaldehyde level above 40 M inhibited cell multiplication and elevated SCE considerably. A high acetaldehyde level is thought to elicit the fetal alcohol syndrome, a view supported by clinical and experimental observations.     

The AA and ANA rat lines, selected for differences in voluntary alcohol consumption

The offspring of rats that voluntarily select larger quantities of alcohol are heavier consumers of alcohol than the offspring of rats that tend to avoid it. Such selective breeding, repeated over many generations, was used to develop the AA (Alko, Alcohol) line of rats which prefer 10% alcohol to water, and the ANA (Alko, Non-Alcohol) line of rats which choose water to the virtual exclusion of alcohol. In addition to demonstrating the likely role of genetic factors in alcohol consumption, these lines have been used to find behavioral, metabolic, and neurochemical correlates of differential alcohol intake. Some of the line differences that have been found involve the reinforcing effects of ethanol, the changes in consumption produced by alcohol deprivation and nutritional factors, the behavioral and adrenal monoamine reactions to mild stress, the development of tolerance, the accumulation of acetaldehyde during ethanol metabolism, and the brain levels of serotonin. It is hoped that these studies will lead to a better understanding of the genetically-determined mechanisms that influence the selection of alcohol.     

The AA and ANA rat lines,selected for differences in voluntary alcohol consumption

Summary The offspring of rats that voluntarily select larger quantities of alcohol are heavier consumers of alcohol than the offspring of rats that tend to avoid it. Such selective breeding, repeated over many generations, was used to develop the AA (Alko, Alcohol) line of rats which prefer 10% alcohol to water, and the ANA (Alko, Non-Alcohol) line of rats which choose water to the virtual exclusion of alcohol. In addition to demonstrating the likely role of genetic factors in alcohol consumption, these lines have been used to find behavioral, metabolic, and neurochemical correlates of differential alcohol intake. Some of the line differences that have been found involve the reinforcing effects of ethanol, the changes in consumption produced by alcohol deprivation and nutritional factors, the behavioral and adrenal monoamine reactions to mild stress, the development of tolerance, the accumulation of acetaldehyde during ethanol metabolism, and the brain levels of serotonin. It is hoped that these studies will lead to a better understanding of the genetically-determined mechanisms that influence the selection of alcohol.     

Neuritic plaque-like structures in the rat cerebellum following prolonged alcohol consumption

Primitive neuritic plaques were observed in the inner third of the molecular layer of the cerebellar cortex of rats following chronic alcohol consumption. Neurites were identified as dystrophic parallel fiber boutons. Amyloid material dispersed among neurites was not clearly recognized, dystrophic some fibrils were frequently seen among them. Astrocytic processes were noted in the periphery of the plaque. Microglial reaction, however, was non-existent. The rarity of these lesions in the rat cerebellum and their probable relation to long periods of alcohol consumption is discussed.     

Long-lasting persistence of elevated sister-chromatid exchange frequencies induced by perinatal benzo(a)pyrene treatment in rat bone-marrow cells

In this work the possibility that a mutagenic factor acting in utero or in the perinatal period might lead to elevated mutagenic rates in bone-marrow cells after a considerable period of time was examined. An aromatic hydrocarbon, benzo(a)pyrene was used as the test substance. Benzo(a)pyrene treatments resulted in significantly higher sister-chromatid exchange (SCE)-frequencies in both fetal and neonatal groups in both sexes, even four months after exposure. In a second experiment we examined whether mutagenic exposure suffered in utero could make the individual more susceptible to mutagenic effects in adulthood. Preliminary results indicate that such a possibility could exist.     

重庆地区冠心病危险因素分析

目的探讨重庆地区冠心病的危险因素及其与冠心病的关系,为本地区冠心病的防治和干预提供科学依据。方法选择疑似冠心病患者458例,根据临床资料和冠状动脉造影分为冠心病组和非冠心病组,分析危险因素和冠心病的关系。结果 (1)冠心病组男性、高龄、吸烟、高血压、糖尿病和血脂紊乱的比例明显高于非冠心病组(P0.05)。(2)男性冠心病组吸烟、高血压和糖尿病的比例明显高于非冠心病组(P0.05);女性冠心病组高龄、高血压和血脂紊乱明显高于非冠心病组(P0.05)。(3)低龄组冠心病男性、吸烟、高血压、糖尿病和血脂紊乱的比例显著高于非冠心病组(P0.05);高龄组冠心病高血压和糖尿病比例显著高于非冠心病组(P0.05)。结论多因素Logistic回归分析显示:年龄、性别、吸烟、高血压、糖尿病和血脂紊乱是重庆地区冠心病的最显著的危险因素。     

Cellular and molecular mechanisms of alcohol-induced osteopenia

Alcoholic beverages are widely consumed, resulting in a staggering economic cost in different social and cultural settings. Types of alcohol consumption vary from light occasional to heavy, binge drinking, and chronic alcohol abuse at all ages. In general, heavy alcohol consumption is widely recognized as a major epidemiological risk factor for chronic diseases and is detrimental to many organs and tissues, including bones. Indeed, recent findings demonstrate that alcohol has a dose-dependent toxic effect in promoting imbalanced bone remodeling. This imbalance eventually results in osteopenia, an established risk factor for osteoporosis. Decreased bone mass and strength are major hallmarks of osteopenia, which is predominantly attributed not only to inhibition of bone synthesis but also to increased bone resorption through direct and indirect pathways. In this review, we present knowledge to elucidate the epidemiology, potential pathogenesis, and major molecular mechanisms and cellular effects that underlie alcoholism-induced bone loss in osteopenia. Novel therapeutic targets for correcting alcohol-induced osteopenia are also reviewed, such as modulation of proinflammatory cytokines and Wnt and mTOR signaling and the application of new drugs.     

Influence of pulsing electromagnetic field on the frequency of sister-chromatid exchanges in cultured mammalian cells

Exposures of Chinese hamster cells to pulsing electromagnetic field (PEMF) with 0.18-2.5 mT did not influence the baseline frequency of sister-chromatid exchanges (SCE). The results suggest that PEMF with the magnetic intensity examined does not interfere with DNA replication nor produce DNA lesions, thereby leading to an increased frequency of SCE.     

Neuritic plaque-like structures in the rat cerebellum following prolonged alcohol consumpotion

Summary Primitive neuritic plaques were observed in the inner third of the molecular layer of the cerebellar cortex of rats following chronic alcohol consumption. Neurites were indentified as dystrophic parallel fiber bouton. Amyloid material dispersed among neurites was not clearly recognized, dystrophic some fibrils were frequently seen among them. Astrocytic processes were noted in the periphery of the plaque. Microglial reaction, however, was non-existent. The rarity of these lesions in the rat cerebellum and their probable relation to long periods of alcohol consumption is discussed.This work was granted by I.N.I.C., project MbPl, and Stiftung Volkswagenwerk, project I/37424.     

Influence of pulsing electromagnetic field on the frequency of sister-chromatid exchanges in cultured mammalian cells

Summary Exposure of Chinese hamster cells to pulsing electromagnetic field (PEMF) with 0.18–2.5 mT did not influence the baseline frequency of sister-chromatid exchanges (SCE). The results suggest that PEMF with the magnetic intensity examined does not interfere with DNA replication nor produce DNA lesions, thereby leading to an increased frequency of SCE.     

Enhancement by caffeine of sister-chromatid exchange frequency induced by antineoplastic agents in human lymphocytes.

The SCE frequency induced by Thiotepa and the effect of this antineoplastic drug in combination with caffeine have been studied in cultures of human peripheral blood. Caffeine was found to enchance SCE and breakage frequencies induced by Thiotepa in human lymphocytes.     

Enhancement by caffeine of sister-chromatid exchange frequency induced by antineoplastic agents in human lymphocytes

Summary The SCE frequency induced by Thiotepa and the effect of this antineoplastic drug in combination with caffeine have been studied in cultures of human peripheral blood. Caffeine was found to enhance SCE and breakage frequencies induced by Thiotepa in human lymphocytes.Acknowledgment. I am deeply grateful to Dr M.J.W. Faed, for stimulating discussions, guidance and constructive criticism. This paper is a part of my Ph.D. thesis submitted to Dundee University.     

Effect of chronic ethanol treatment on peroxisomal acyl-CoA oxidase activity and lipid peroxidation in rat liver and heart

Chronic ethanol administration was shown to increase catalase and acyl-CoA oxidase activities in rat myocardium but did not alter the activity of liver peroxisomal enzymes. As a result of alcohol consumption a 2-3-fold increase in the level of lipid peroxidation was observed in the heart tissue while in the liver the induction was much less pronounced.     

Oxygen consumption and biosynthetic function in perfused liver from rats at different stages of development

Changes in mitochondrial function were studied in perfused liver from rats aged 24 – 365 days. Oxygen consumption together with the rates of gluconeogenesis, urea synthesis and ketogenesis were determined. Basal mitochondrial respiration as well as the ability of the liver to synthesize glucose, urea and ketone bodies declined from 24- to 365-day-old rats. On the other hand, on transition from 24 to 60 days the liver oxidation rate of hexanoate, sorbitol and glycerol is enhanced, but not of ketone bodies or palmitate. Our results show that the transition from weaning to middle age is accompanied by defined changes in hepatic substrate oxidation. From the observed time course of the decrease in basal and substrate-stimulated oxygen consumption, it is concluded that in rat liver cells a decline in respiratory chain function, long-chain fatty acid and ketone body metabolism, gluconeogenesis and ureogenesis occurs at a relatively early life stage. Received 19 June 1998; received after revision 11 September 1998; accepted 11 September 1998