摘要:

AbstractThe present study assesses the contribution of genetic and environmental factors to variability in placental aryl hydrocarbon hydroxylase and glutathione transferase activities using twin study methodology. Twin placentas were collected at the time of delivery. The placenta, except for a single layer of maternal decidua, consists of fetal tissue exhibiting fetal genotype. Microsomal and cytosolic fractions were prepared under stringent protocols to prevent enzyme activity loss. There were two monozygotic‐monochorionic pairs, five monozygotic‐dichorionic pairs, and 21 dizygotic‐dichorionic pairs that showed measurable aryl hydrocarbon hydroxylase activity using the direct fluorometric assay. Most of the mothers were smokers. Aryl hydrocarbon hydroxylase activity was measured with two different substrates, benzo(a)pyrene and 7‐ethoxyresorufin. Glutathione transferase activity was measured using glutathione and 1‐chloro‐2,4‐dinitrobenzene as substrates for a spectrophotometric assay that follows the conversion of the aromatic substrate. Twin pair similarity was calculated with intraclass correlation coefficients. There is a high correlation between the activities of the two aryl hydrocarbon hydroxylase substrates (r = .814), but no correlation between aryl hydrocarbon hydroxylase and glutathione transferase activity levels. There is little evidence of genetic variability underlying the variation in the enzyme activities because monozygotic‐dichorionic twins are no more similar to each other for the three substrate activities than are the dizygotic twins. To delineate the prenatal environmental influences on placental enzyme variability, dichorionic placentation was subdivided further into contiguous and noncontiguous placental position. Lower intraclass correlation coefficients are obtained for the dizygotic twins whose placentas were noncontiguous compared with dizygotic twins with contiguous placentas. The results suggest that most of the variability seen in these placental enzyme systems is due to environmental differences within uteri, rather than genetic variability in the population. This does not negate the possibility that between‐pair, or population, variability may have a genetic component, because even dizygotic twins share a large proportion of their genes. This study points out that a significantly variable environment exists within

ISSN:0270-3211    

DOI:10.1002/tcm.1770060402

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

年代:1986

数据来源: WILEY

摘要:

AbstractAmong the steroid molecules, bile acids have been shown to have either a co‐ or an antimutagenic activity toward various direct and indirect acting mutagens in the Ames test. The present report extends such observations to other steroids having hormonal activity. The main effect of the active hormones is an inhibition of the genotoxicity of both direct and indirect acting mutagens. This effect is strictly structure‐related. Moreover, both ethinyl oestradiol and mestranol, which are synthetic derivatives of β‐oestradiol largely used in contraceptive pills, are strong inhibitors of the mutagenicity, acting at nanomolar concentrations.The present article emphasizes the possible role of compounds with steroid structure as modulators of genoto

ISSN:0270-3211    

DOI:10.1002/tcm.1770060403

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

年代:1986

数据来源: WILEY

摘要:

AbstractFurther evidence is reported here of genetic and developmental damage that can be induced by a sublethal pH decrease. The effects of three inorganic acids (HCl, H2SO4, and H3PO4) on embryos and sperm from the sea urchinsSphaerechinus granularisandParacentrotus lividuswere evaluated. In addition, acidification of the medium was tested for spontaneous reversion to His+prototrophy inSalmonella typhimurium(strains TA97, TA98, TA100, TA102, TA1535) up to toxic levels, by both liquid incubation and agar plate incorporation.The induction of developmental and mitotic abnormalities inS. granularisconfirmed our previous observations onP. lividus. Embryotoxicity was exerted inS. granularismore severely by H3PO4than by HCl or H2SO4(pH 7 to 6), while the induction of mitotic abnormalities appeared at a pH of ≤ 6.5 irrespective of the acids used. By suspendingS. granularisorP. lividussperm in acidified filtered seawater (fsw) and then inseminating the eggs in natural fsw (pH = 8.0), the offspring showed developmental and mitotic abnormalities. Low‐pH‐induced spermiotoxicity was ruled out in our experiments, since fertilization success of acid‐exposed sperm was actually enhanced, as compared to sperm suspended in untreated fsw.The exposure ofS. typhimuriumto different pH's (ranging from 4 to 9) invariably failed to induce any changes in reversion rates, regardless of the acids (or alkali) being used.These results suggest that extracellular acidification may cause sublethal damage that in turn leads to an impairment of mitotic activity and cell differen

ISSN:0270-3211    

DOI:10.1002/tcm.1770060404

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe tolerance ofDrosophila melanogasterto heavy metal compounds was investigated with special emphasis on methylmercury. A pronounced variation in tolerance to CH3HgOH, HgCl2, (C2H5)3PbCl, (CH3)3SnCl, and CdCl2was recorded between 12 wild‐type strains. After ranking the tolerance of the strains with respect to the five compounds rank correlations for experiments within and between compounds were calculated. The results showed a high degree of correlation within compounds but no unequivocal indication of a correlation between compounds, indicating that different mechanisms of genetic control for tolerance were operating for the five compounds. Rank correlations for experiments with 12 different mercury, lead, tin, and cadmium compounds and the same 12 wild‐type strains only indicated one significant correlated response, between tripropyltin and tributyltin.A selection experiment for tolerance to methylmercury was performed with a foundation population, synthesized from four wild‐type strains, showing a high initial tolerance. One control and two levels of treatment doses were used. A distinct selection response was obtained and a high tolerance was reached particularly for the high‐dose selection line after 12 generations, when the experiment ended. Genetic analysis of the tolerance indicated a dominant and polygenic inheritance. Investigation of the uptake and excretion of CH3Hg203OH showed that the level of tolerance to methylmercury was correlated with the uptake of the mercury but apparently not with the rate of excretion.Cystein increased the susceptibility to methylmercury. Inorganic mercury and trimethyl lead exhibited a synergistic toxic effect, evidently as the result of an in vitro transmethylation of mercury.A high somatic susceptibility to methylmercury also applied to the induction of nondisjunction and sex‐linked recessiv

ISSN:0270-3211    

DOI:10.1002/tcm.1770060405

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe metabolism of benzo(a)pyrene [B(a)P] to organic soluble and water soluble metabolites by transformable C3H10T1/2CL8 mouse embryo fibroblasts was studied as a function of time, B(a)P concentration, and cell density. The total formation of organic‐soluble and water‐soluble metabolites increased with incubation time from 4 to 48 h and with B(a)P concentration from 4 to 40 μM. As cell density increased, the metabolic rate decreased for organic‐soluble and water‐soluble products between 6,300 and 54,000 cells/cm2probably due to decreases in B(a)P concentrations to values below saturation. Specific organic‐soluble metabolites identified were B(a)P‐pre‐9, 10‐diols, B(a)P‐9,10‐diol, B(a)P‐7,8‐diol, B(a)P‐3,6‐quinone, B(a)P‐3‐phenol, and B(a)P‐9‐phenol. Water‐soluble metabolites were subjected to enzymatic hydrolysis with β‐glucuronidase and aryl sulfatase to identify specific conjugated products. The sulfate conjugated metabolites identifed were B(a)P‐7,8‐diol, B(a)P‐pre‐9, 10‐diols, B(a)P‐9, 10‐diol, and B(a)P‐3, 6‐quinone. The β‐glucuronic acid metabolites identified were B(a)P‐pre‐9, 10‐diols, B(a)P‐3, 6‐quinone, and B(a)P‐3‐phenol. Patterns of metabolite formation rates are discussed as to their possible effect on morphological transformati

ISSN:0270-3211    

DOI:10.1002/tcm.1770060406

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe sister chromatid exchange (SCE) assay in bone marrow and spleen cells of Chinese hamsters was used to evaluate the differences between in vivo and in vivo/in vitro (exposure of animals to chemical followed by culturing of cells) conditions. Cyclophosphamide, a mutagenic carcinogen, caused dose‐related SCEs both in vivo and in vivo/in vitro. In the in vivo group, both bone marrow and spleen cells showed approximately a five‐fold increase in SCEs over controls following 40 mg cyclophosphamide/kg treatment. The same dose, under in vivo/in vitro conditions, caused about three‐ and six‐fold increases in SCEs over controls in bone marrow and spleen cells, respectively. While the extent of cyclophosphamide‐induced SCEs (after subtraction of baseline level) in bone marrow is approximately the same under both conditions, the response was significantly higher in spleen cells in vivo/in vitro than in vivo. Under in vitro conditions, treatment of bone marrow and spleen primary cell cultures with a direct acting mutagen, trinitrofluorenone, caused significant dose‐related increases in SCEs in both cell types in an equivalent manner. The replicative indices under these experimental conditions remained almost the same. Thus, this study indicates the potential usefulness of Chinese hamster bone marrow and spleen cells for in vivo and in vitro comparative studies with the same tissue to better assess the genotoxic hazard o

ISSN:0270-3211    

DOI:10.1002/tcm.1770060407

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe effects of murine cytomegalovirus (MCMV) on the prenatal development of the CD‐1 mouse were investigated. Two sets of experiments were performed. In the first, mice were inoculated with different doses of MCMV on gestational day 7, and in the second, pregnant animals were inoculated with a subacute injection dose at different gestational stages. The effects of maternal infection on pregnancy in terms of maternal sickness, embryo lethality, date of parturition, litter size, postnatal death, and pups' body weight on d 1 and d 3 postpartum were investigated. High‐dose MCMV infection on d 7 of pregnancy resulted in a significant increase in early embryo resorption and also in a reduction of the neonatal body weight of surviving pups. Two gestational stages were identified as being especially susceptible to MCMV infection. Most embryonic death as indicated by resorption rates was found after treatment on d 9, whereas perinatal death was most frequent when treatment was done on d 13 of gestation. Still births and neonatal death within 24 h of birth were found commonly in this latter group, which also showed the most pronounced growth retardation. The phenomenon of delay in time of parturition was noted and found to be most significant in groups of animals that were inoculated on d 3 or d 13. This investigation suggests that the effects of MCMV on the CD‐1 mouse vary greatly with the age of the embryo and the course of the infe

ISSN:0270-3211    

DOI:10.1002/tcm.1770060408

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe effects of maternal exposure to nitrofen or protein‐energy malnutrition on the number and sizes of cells in selected organs of the fetal rat have been studied. Pregnant rats were fed either an adequate (CON) or protein‐energy deficient diet (PEM) throughout gestation. Each diet group was divided into two subgroups. One subgroup was gavaged with 25 mg nitrofen/kg body weight on gestational days 7–21 and the other, with corn oil carrier only. Fetal liver, kidneys, intestine, heart, lung, and brain were weighed and assayed for DNA, RNA, and protein. Maternal protein deficiency resulted in a reduction in organ weight and total DNA, RNA, and protein in all six organs. Maternal nitrofen exposure resulted in reduced weight and reduced protein in all organs except the brain. Total DNA and RNA were reduced in intestine, heart, and lung, and total RNA was also reduced in the liver following maternal nitrofen exposure. An interaction between diet and toxin affected lung weight, DNA, RNA, and protein, intestinal total protein, and heart DNA. Protein/DNA ratios were reduced in liver, intestine, and brain in the group fed the inadequate diet and in intestine only following nitrofen exposure. The deficient diet resulted in increased RNA/DNA ratio in the fetal liver and heart and a decreased ratio in the kidney and brain. Nitrofen exposure resulted in a lower RNA/DNA ratio in the liver. The data indicate that maternal protein‐energy malnutrition results in smaller organs in the fetuses with fewer cells and containing less protein and RNA. The greater reduction in protein than that expected from the decrease in numbers of cells in the liver, intestine, and brain in fetuses of malnourished dams suggests that cells were also smaller. Effects on RNA/DNA were essentially in the same direction as seen for protein/DNA. In general, the diet deficiency appeared to have a general metabolic effect reducing cell replication that, however, spared the brain. Nitrofen exposure results in an organ‐specific reduction in cell replication in the intestine, heart, and lung. An interaction between restricted diet and nitrofen exposure involves the lung

ISSN:0270-3211    

DOI:10.1002/tcm.1770060409

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

年代:1986

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770060410

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

年代:1986

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770060401

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

年代:1986

数据来源: WILEY