摘要:

AbstractThe susceptibility of chick embryos to the teratogenic action of intraamniotically injected hydrocortisone increases by several orders during the first four days of incubation. An attempt was made to correlate this phenomenon with the appearance of specific intracellular binding proteins for glucocorticoids. The binding of [3H] corticosterone to the soluble cytoplasmic proteins of the chick embryo was investigated on days 1.5, 2, 3, and 4 of incubation using a gel filtration method. No evidence of high affinity binding was found in embryos on day 1.5. High affinity binding of [3H] corticosterone to the cytosol proteins was first observed in embryos on day 2, but the binding capacity was four times lower than that found in embryos on days 3 and 4. A correlation was obtained between the increasing sensitivity of the chick embryo to hydrocortisone and the appearance of the intracellular binding protein for glucocorticoids. The causal relationship between these two phenomena is further supported by the finding that administration of a nonteratogenic dose of cortexolone completely prevents the teratogenic “cleft beak” action of hydrocortisone, presumably on the basis of competition for binding sites to the glucocorticoid receptor. These findings are consistent with the hypothesis that the teratogenic action of glucocorticoids is mediated by specific cytoplasmic receptors in the chick emb

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:1<1::AID-TCM1770030102>3.0.CO;2-Q

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

年代:1983

数据来源: WILEY

摘要:

AbstractThere is a direct relationship between the metabolism and mutagenicity of N‐nitro‐sohexamethyleneimine (NO‐HEX) in the presence of uninduced and AC‐ and PB‐induced S8and S9fractions from rats and hamsters. Although α‐hydroxylation is the most important process in the formation of mutagens, NO‐HEX may be hydroxylated on the β‐ and γ‐carbon atoms as well. β‐ and γ‐hydroxyNO‐HEX do not appear to play a significant role in the total mutagenicity of NO‐HEX. Using rat liver subcellular fractions, β‐ and γ‐hydroxyNO‐HEX are only marginally mutagenic compared with NO‐HEX. With hamster S9fractions, β‐hydroxyNO‐HEX is equally as mutagenic as NO‐HEX itself, but γ‐hydroxyNO‐HEX is a much less potent mutagen. However, β‐hydroxyNO‐HEX is produced in small amounts and therefore does n

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:1<9::AID-TCM1770030103>3.0.CO;2-F

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe dominant lethal test and the spermatocyte test were used to assess the mutagenic effect of morphine sulphate in male mice. Pregnant females were examined at midterm for the number of corpora lutea and intrauterine contents. The effect of the drug on total embryonic losses was very marked at the 1‐, 2‐, 3‐, and 6‐week mating intervals. However, the effect of morphine treatment was much more marked and consistent on preimplantation deaths than on early deaths. The consistently high mutation indices (MI) obtained in different treatment groups implied that morphine specifically affected the early spermatid stage (MI 30, 46, 77, and 31 for the groups treated with 10, 20, 40, and 60 mg morphine, respectively). High mutation indices in the range of 20–36 were shown by a few other spermatogenic stages but were not systematically exhibited by all groups.The spermatocytes of a second group of treated males were examined 45–50 days after treatment with either morphine or saline. The cytogenetic analysis of spermatocytes at diakinesis‐metaphase 1 showed significant increases in the frequency of multivalent configuration, translocation, and autosomal and sex chromosome univalents in the groups treated with morphine, compared with the spontaneous rates of the control group. In general, the different doses of morphine resulted in a total chromosomal aberration frequency of approximately 3–6 times the control value, demonstrating nearly a linear dose‐response relationship.The results obtained from both test systems in the mouse suggest that morphine in the doses given is potentially mutagenic in this species and can induce sustained chromosomal aberrations in

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:1<19::AID-TCM1770030104>3.0.CO;2-Y

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

年代:1983

数据来源: WILEY

摘要:

AbstractCarcinogens from different chemical series were tested on the wild‐type allele of the complex white (w+) locus, which comprised some 5 recombinational subunits, the proximal part (w 4.5+) exhibiting regulatory interactions with the neighbouring gene zeste (z). Three w+loci were used, with different proximal regulatory sequences, including an unstable locus with a TE. Altered expression with each z w+complex was assayed on the basis of the induction of aberrantly pigmented eye sectors known to be diagnostic of the interaction between z and the dosage of the functionally active w 4.5+subunits.All the tested carcinogens (DMN, DMBA and AFB1) were poorly active in the induction of the putative somatic deletions causing white (w−) eye sectors. In contrast, they were highly effective on the regulatory w 4.5+sequences in all test loci, as indicated by the significantly higher yield of red eye sectors (w 4.5−) above the controls. However, this effect varied as a function of the chemical structure of the test compound and the genetic organisation of the regulatory targets.Germinal mutagenicity of the test compounds was assayed on X chromosomes carrying stable and unstable w+loci, after the injection of adults and topical application on newly hatched larvae. Both techniques revealed that there was no association between the induction of somatic alterations in gene expression and the germinally induced mutations, including the TE w 4.5+deletions. Furthermore, the somatic events, unlike mutations, showed an association with the time of genetic determination during eye‐disc cell differentiation.The present results were compatible with the concept of somatic gene misregulati

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:1<27::AID-TCM1770030105>3.0.CO;2-U

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe organospecific activity of the N‐nitroso compounds diethylnitrosamine (DEN), dibutylnitrosamine (DBN), N‐nitroso‐piperidine, N‐methyl‐N‐nitrosourethane (NMUT), N‐methyl‐N‐nitroso‐urea (NMU), and N‐methyl‐N′‐nitro‐N‐nitroso‐guanidine (MNNG) has been studied in the host‐mediated assay by recovering yeast cells present in testes, liver, and lung of rats.All six substances were genetically active, and their organospecificity under host‐mediated assay conditions corresponded relatively well to their organospecific carcinogenic effects of single dose experiments, but n

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:1<41::AID-TCM1770030106>3.0.CO;2-R

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

年代:1983

数据来源: WILEY

摘要:

AbstractTwenty‐five 5‐nitroimidazole and two 5‐nitrothiazole derivatives were tested for mutagenicity as well as for antibacterial activity inSalmonella typhimunumTA‐100 strain. Many of these compounds such as metronidazole, azanidazole, nimorazole, carnidazole, ornidazole, tinidazole, etc are extensively used in human chemotherapy, and some of them were recently synthetized for possible clinical trials as hypoxic cell specific radiosensitizers. Both mutagenic and antibacterial activity were shown for 22 of the test compounds. The high correlation between mutagenic and antibacterial activity supports the hypothesis of a same mechanism for both activities. The present results confirm that the mutagenicity of the nitroheterocyclic compounds is not separated from other biological activities, such as antimicrobial a

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:1<51::AID-TCM1770030107>3.0.CO;2-L

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe mutagenicity of the vicinity of an oil‐refining complex and a petrochemical complex was examined using the germinal revertant frequency ofZea mayswaxy‐C W22 and the somatic stamen hair system ofTradescantia. A 3‐year study was conducted at Wood River, Illinois, in 1978, 1979, and 1980, and a 1‐year study in 1979 at Beaumont, Texas. The studies conducted in 1978 registered the effects of airborne pollutants and possible soil pollutants. The studies in 1979 and 1980 registered only the effects of airborne pollutants. Elevated mutation frequencies ofZea mayscompared to various controls occurred in 1978, 1979, and 1980 at both complexes. The mutation frequencies ofZea mayswere particularly high, up to 26‐times control values. By contrast, the mutation frequencies ofTradescantiawere much lower, with maximum mutation frequencies five times cont

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:1<65::AID-TCM1770030108>3.0.CO;2-B

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

年代:1983

数据来源: WILEY

摘要:

AbstractIn vivo and in vitro methodologies that have employed the yeastSchizosaccharomyces pombeas genetic indicator have been utilized to investigate the mutagenicity of two trichloroethylene (TCE) samples of pure and technical grade. Mutagenicity assays were also performed on two stabilizers contained in the technical grade sample: epichlorohydrin and 1,2‐epoxybutane.In the in vitro studies a metabolic conversion system was supplied by liver homogenate (S‐9) from mice and rats untreated and pretreated with phenobarbital and/or β‐naphthoflavone. Up to highly toxic doses of TCE were applied to growing and stationary‐phase yeast cells.In the in vivo studies two different host‐mediated assays, intrasanguineous and intraperitoneal methodologies, were performed on different mice breeds treated by oral administration.Epichlorohydrin and epoxybutane were tested singly or combined in a mixture of the same ratio as in the technical grade TCE sample.Both TCE samples gave negative results for in vivo and in vitro assays, whereas the two contaminants were found mutagenic only in vitro. The high toxicity of the technical TCE sample did not allow us to reach concentrations containing effective levels of its two

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:1<75::AID-TCM1770030109>3.0.CO;2-5

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

年代:1983

数据来源: WILEY

摘要:

AbstractMercuric chloride, methylmercuric chloride, and cadmium chloride directly affect the human placental syncytiotrophoblast microvillous membrane. These heavy metals alter the facilitated diffusion of α‐aminoisobutyric acid (AIB) into vesicles of this membrane in μM concentrations. Mercuric chloride abolishes temporal kinetics of AIB transport, inducing an initial increase in AIB transport (27% at 100 μM) but subsequently lowering equilibrium values when compared to equilibrium time points in control. Methylmercuric chloride and cadmium chloride inhibited the initial rate of AIB transport (40% and 21%, respectively, at 200 μM), but did not affect the equilibrium value of AIB transported when compared to equilibrium levels in control. These effects were concentration dependent. Methylmercuric chloride was more potent in inhibiting AIB transport than cadmium chloride. Methylmercuric chloride and cadmium chloride effects on AIB transport were observed with minimal preincubation with placental vesicles. However, preincubation was necessary for mercuric chloride‐induced perturbation of AIB transport. Cysteine protects against mercuric chloride‐ and methylmercuric chloride‐induced effects on AIB transport but did not reverse these perturbations. Mercury‐ and cadmium‐induced placental membrane toxicity result from interactions of these heavy metals with the placental p

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:1<89::AID-TCM1770030110>3.0.CO;2-O

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

年代:1983

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:1<::AID-TCM1770030101>3.0.CO;2-I

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

年代:1983

数据来源: WILEY