摘要:

AbstractAqueous extracts of tar from a coal gasification electrostatic precipitator were tested for its toxic and teratogenic potential in vitro on embryos of the amphibian Xenopus laevis. The 96‐h LC50and EC50were determined to be 0.83% and 0.48%, respectively. The developmental stage of normal‐appearing exposed embryos is not affected by increasing concentrations of the extract. Embryo growth, however, is significantly reduced at concentrations as low as 0.25%. Motility and pigmentation were effectively reduced relative to controls by extract concentrations of 0.5% and greater. Exposed embryos are shorter and stockier than controls. Malformations of head, eyes, viscera, and spine are common, and cartilage formation is abnormal. The epidermis is often hyperplastic, and large blisters occur over the somatic surface. The severity of abnormal development is directly related to the concentration of the toxicant to which the embryos are exposed. Chemical analysis shows that the aqueous extracts contain phenols, furans, monoaromatic and diaromatic hydrocarbons, and mono‐ and diazaarenes and/or monoaromatic a

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:1<1::AID-TCM1770020102>3.0.CO;2-U

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

年代:1982

数据来源: WILEY

摘要:

AbstractAssessment of mammalian sperm acrosomal proteolytic activity, sperm motility, and sperm count may be useful for detecting mutagens, carcinogens, developmentally active agents, and antifertility effects.Groups of six albino mice were given a single i.p. injection of 5 mg/kg mitomycin C (MC) or saline. One treated and one control group of mice were killed 1, 3, 5, 7, or 10 weeks later. Sperm extracted from the vasa deferentia at these killing times were derived from cells treated as spermatozoa, spermatids, preleptotene—late spermatogonial cells, spermatogonial cells, and spermatogonial stem cells. In sperm derived from treated preleptotene or spermatogonial cells, the sperm count, sperm motility, and acrosomal proteolytic activity were decreased significantly. Acrosomal proteolytic activity was also decreased in sperm from spermatogonial stem cells. None of these sperm phenotypes were decreased in treated spermatozoa and spermatids.We propose the hypothesis that induced loss of sperm motility and acrosomal proteolytic activity in single spermatozoa derived from MC‐treated spermatogonial cells is caused by mutational or developmental effects, whereas in preleptotene‐derived and late‐spermatogonium‐derived sperm similar dysfunction results from developmental effects. Our data support the hypothesis indirectly.Since a low sperm count is correlated with decreased fertility and acrosomal proteolytic activity is essential for penetration of the zona pellucida by the sperm, the presence of these sperm phenotypes may help to detect chemicals with antifertilit

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:1<13::AID-TCM1770020103>3.0.CO;2-C

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

年代:1982

数据来源: WILEY

摘要:

AbstractBecause of its suitability for genetic studies, the nematodeCaenorhabdiris eleganswas examined for its responsiveness to the phorbol esters. Phorbol 12‐myristate 13‐acetate had three effects. It inhibited the increase in animal size during growth; it decreased the yield of progeny; and it caused uncoordinated movement of the adult. The effects on nematode size, progeny yield, and movement were quantitated. Concentrations of phorbol 12‐myristate 13‐acetate yielding half‐maximal responses were 440, 460, and 170 nM, respectively. As was expected from the biological responsiveness of the nematodes, specific, saturable binding of phorbol ester to nematode extracts was found. [3H]phorbol 12,13‐dibutyrate bound with a dissociation constant of 26.8 ± 3.9 nM. At saturation, 5.7 ± 1.4 pmole/mg prot

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:1<19::AID-TCM1770020104>3.0.CO;2-3

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

年代:1982

数据来源: WILEY

摘要:

AbstractA mechanistic link between teratogenesis and carcinogenesis has been suggested by a wide variety of scientific observations. This report attempts to provide a theoretical explanation for one of the several possible mechanisms which might be shared during carcinogenesis and teratogenesis. The initiation and promotion concept of carcinogenesis was briefly reviewed and the role of intercellular communication during the complex tumor promotion phase was discussed. Inhibition of intercellular communication by a wide variety of physical, chemical and biological factors was speculated to disrupt the regulation of proliferation and differentiation in stem cells. Chemicals, which interfered with intercellular communication during early organogenesis, have the potential of being teratogens, while if they are present in the developed, initiated organisms have the potential of being tumor promoters. Evidence was presented showing that known tumor promoters which inhibited intercellular communication also had been shown to be teratogens. It was concluded thatin vitroassays, designed to measure intercellular communication, although having known limitations, might be used as anin vitromeans to screen for potential teratogens.

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:1<31::AID-TCM1770020105>3.0.CO;2-2

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

年代:1982

数据来源: WILEY

摘要:

AbstractMany teratologic investigations have shown that certain types of chemical insults to the embryo (those altering replication, transcription, and translation) can cause excessive cell death in tissues destined to become malformed. Chemical carcinogens also induce cell death in target tissues, but the critical event is believed to be heritable alteration in the DNA of surviving cells. In the present study, an attempt was made to study the interaction between cell death and DNA damage in the initiation of birth defects. The pattern of DNA damage induced by cyclophosphamide was examined at time intervals before, during, and after the necrotic episode in mouse embryo limb buds. The alkaline elution assay was used to measure alkali‐labile sites in single‐strand DNA due to its adaptability to small tissue samples.An ip dose of 20 mg/kg of cyclophosphamide induced forelimb malformations in 85% of surviving mouse fetuses and 30% embryolethality when administered at 9 am on Day 11. As early as 5 hr after exposure, a slight excess of necrosis was observed in treated limbs by light microscopy, while at 24 hr, massive necrosis was evident. By 48 and 72 hr, excess necrosis was not observed in treated limbs. When alkaline elution analysis was conducted at prenecrotic (1‐, and 5‐hr), necrotic (24‐hr), and postnecrotic (48‐, and 72‐hr) intervals, a trend toward increasing DNA damage in treated limbs with time was observed. The greatest differences in elution values occurred during the postnecrotic period. Although mean retention values were not significantly different, significantly increased variance was obtained in retention values of treated limbs at all time intervals other than 1 hr. This may reflect the actual in vivo situation where relatively few cells within a heterogeneous population of cells carry sublethal DNA damage into the postnecrotic period. These results suggest that not all limb bud cells affected by teratogenic exposure to cyclophosphamide die, but that some persist to the postnecrotic period carrying heritable alterations

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:1<47::AID-TCM1770020106>3.0.CO;2-R

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

年代:1982

数据来源: WILEY

摘要:

AbstractTeratogenicity tests should provide answers to three questions: (1) Can the agent induce developmental defects? (“teratogenic potential”); (2) What are the effective doses? (“teratogenic potency”); and (3) Are effective doses below adult toxic doses? (“teratogenic hazard”). The answers to (2) and (3) should be quantitative in nature, but there are no accepted parameters to express these properties. In this paper we propose parameters for the description of teratogenic potency and hazard in quantitative terms. Derivation and calculation of the parameters are illustrated by the analysis of adult lethality and teratogenicity data of eight structurally related anhydrides and imides, following testing in the CD‐1 mouse. Teratogenicity was evaluated following treatment on Days 8–10 of gestation, using an average of four dose groups per compound and at least 10 dams per group. Adult lethality was estimated following a similar 3‐day dosage schedule with an average of 6 dose groups per compound and at least 8 animals per group. Dose‐response relationships of teratogenicity were fitted to a probit model from which tD50(median effective dose), and other effective doses were computed. It is proposed that tD05, as a minimum teratogenic dose, best represents teratogenic potency. In this study, potency ranged from 0.17 mmol/kg/day for phenytoin to 5.2 mmol/kg/day for ethosuximide. In order to measure teratogenic hazard a ratio between adult toxic (lethality was chosen as the most appropriate measure) and teratogenic responses was made. Since the dose‐response slopes of lethality and teratogenicity were different, a simple ratio between median effective doses could not be used. It is shown that a ratio of LD01to tD05provides a “Relative Teratogenic Index” (RTI) which reflects the teratogenic hazard of a test agent. The following RTIvalues (LD01/tD05) were computed in this study: phthalic anhydride, 0.9; phensuximide, 1.0; succinic anhydride, 1.0; ethosuximide, 1.2; phenytoin, 1.6; phenacemide, 3.3; trimethadione, 4.0; and sodium valproate, 4.1. For these data, tD05and RTI clearly represent the differing teratogenic potencies and hazards of the tested compounds. It is suggested that these parameters may be useful in comparative teratogenicity studies and may be valuable components of developmental

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:1<61::AID-TCM1770020107>3.0.CO;2-O

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

年代:1982

数据来源: WILEY

摘要:

AbstractGravid Wistar rats were treated with either 625 mg/kg of aspirin (acetylsalicylic acid) or vehicle alone on either gestational Day 11 or 12, and their progeny were evaluated postnatally using a standardized series of neurobehavioral tests and physical measurements. The results showed that aspirin given on Day 11 produced maternal and offspring growth deficits not seen when given on Day 12. In addition, aspirin on Day 11 reduced behavioral performance in the progeny on tests of pivoting locomotion, negative geotaxis orientation, home scent (olfactory) orientation, and swimming performance. Further analysis revealed that some of the behavioral effects of aspirin on Day 11 significantly covaried with the body weight reductions noted in this group, such as negative geotaxis, whereas other results showed only minor associations with weight, such as pivoting and swimming. Interestingly, the olfactory orientation results were more apparent after body weight differences were factored out. These data demonstrate that (1) aspirin causes marked differences both in behavior and postnatal growth with only a 24‐hr difference in embryonic age at the time of treatment; (2) behavioral tests are differentially affected by differences in body weight; and (3) behavioral tests appear to be measuring phenomena not reflected by growth, survival, or physical landmarks of development and, as such, add significant information about the toxicological effects of aspiri

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:1<77::AID-TCM1770020108>3.0.CO;2-C

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

年代:1982

数据来源: WILEY

摘要:

AbstractThe frequencies of both spontaneous and mitomycin C (MMC)induced‐ sister chromatid exchanges (SCE) were analyzed in mixed lymphocyte cultures from a kindred with retinoblastoma. Both the affected daughter and male proband, as well as two normal controls, were studied. No differences were observed in the spontaneous or in the MMC‐induced SCE frequencies obtained from the peripheral lymphocytes of these patients compared to the normal controls. Unscheduled DNA synthesis (UDS) was observed in the lymphocytes treated with varying concentrations of both MMC and M‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG). Whereas no differences were observed in the rate of [3H]thymidine incorporation in the retinoblastoma‐derived lymphocytes exposed to MMC when compared to the controls, differences were seen in the response to MNNG. Our data suggest that cells from these retinoblastoma patients respond like normal cells to damage induced by MMC, but that they are unable to repair damage

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:1<85::AID-TCM1770020109>3.0.CO;2-8

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

年代:1982

数据来源: WILEY

摘要:

AbstractThe herbicide 2,4,5‐T (2,4,5‐trichlorophenoxyacetic acid) was evaluated for potential mutagenicity by a Salmonella/mammalian‐microsome test, a dominant lethal test on female rats, and by a cytogenetic assay on spermatogonia of Chinese hamster. In the Salmonella/mammalian‐microsome test on four Salmonella typhimurium strains (TA 1535, TA 100, TA 1537, and TA 98), doses of up to and including 2500 μg/plate did not cause any mutagenic effects. In a dominant lethal test on female rats, 8‐week dietary administration of 2,4,5‐T at doses of up to and including 10 mg/kg/day did not cause any increase in preimplantation loss or the rate of dead implants, and did not have any effect on the fertilization quota. Cytogenetic analysis of the spermatogonia of male Chinese hamsters orally dosed five times at 24‐hr intervals with 2,4,5‐T at levels of up to and including 100 mg/kg did not provide any indication of 2,4,5‐T having chromosome‐damaging effects. Therefore, none of the three test systems provided any indication of 2,4,5‐T hav

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:1<91::AID-TCM1770020110>3.0.CO;2-Z

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

年代:1982

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:1<103::AID-TCM1770020111>3.0.CO;2-T

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

年代:1982

数据来源: WILEY