摘要:

AbstractN‐(4‐hydroxyphenyl)‐all‐trans‐retinamide (HPR) has potential efficacy in the treatment of dermatologic, arthritic, and neoplastic disorders. The teratogenicity of such a compound is of special concern in light of the known adverse effects of retinoids, in general, on the developing conceptus. In these studies, Sprague‐Dawley rats and New Zealand White rabbits were treated orally from gestation days 6 to 15 and 6 to 18, respectively, with 0, 20, 125, or 800 mg/kg/day of HPR.In rat fetuses, low incidences of hydrocephaly (mid‐ and high‐dosage groups) were observed. Fetal tissue (ng/g) and maternal plasma (ng/ml) concentrations of HPR, its major metabolite (N‐[4‐methoxyphenyl] retinamide [MPR]) and retinol were determined in separate groups of similarly‐treated rats 3 h following the last dose on gestation day 15. Fetal tissue concentrations of HPR and MPR were approximately one‐half maternal plasma concentrations. A dose related reduction in maternal plasma and fetal tissue concentrations of retinol were also observed.In mid‐ and high‐dosage rabbit fetuses, a dose‐related increase in the incidence of dome‐shaped head was observed. Subsequent skeletal evaluation revealed delays in skull bone ossification and a widening of the frontal and frontoparietal sutures. Microphthalmia was also observed in two high‐dosage fetuses. A dose‐dependent and statistically significant reduction in maternal plasma retinol levels wa

ISSN:0270-3211    

DOI:10.1002/tcm.1770080102

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

年代:1988

数据来源: WILEY

摘要:

AbstractVasomotor reactivity has been evaluated in rats exposed perinatally and postnatally to thallium sulphate (1 mg/dl in their drinking water ad libitum).Prenatal and postnatal exposure to thallium did not modify the values of the systolic arterial blood pressure on the 30th and 60th day in pups of normotensive and DOCA‐hypertensive rats. The hypertensive responses induced by endosinusal carotid hypotension and by 1‐noradrenaline in pups of normotensive and DOCA‐hypertensive rats, exposed or not exposed to thallium sulphate, were more intensive on the 60th than on the 30th day. Similar effects were observed for the hypotensive responses induced by 1‐isoprenaline and acetylcholine. Prenatal exposure to thallium did not modify hypertensive responses induced by endosinusal carotid hypotension on the 30th and 60th days, but it caused a decrease of hypertensive responses induced by 1‐noradrenaline on the 30th and 60th days and hypotensive responses induced by 1‐isoprenaline and acetylcholine exclusively on the 60th day.Postnatal exposure to thallium did not modify hypertensive responses induced by endosinusal carotid hypotension and hypotensive responses induced by acetylcholine, but it caused a decrease of hypertensive responses induced by 1‐noradrenaline on the 30th and 60th days in pups of normotensive rats and exclusively on the 60th day in pups of DOCA‐hypertensive rats. Moreover, postnatal exposure to thallium caused a decrease of the hypotensive response induced by 1‐isoprenaline exclusively on the 60th day.Our findings show that prenatal and postnatal exposure to thallium sulphate modifies the rat's developing vascular autonomic nervous system with a reduction of the α, β‐adrenergic and muscarinic

ISSN:0270-3211    

DOI:10.1002/tcm.1770080103

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

年代:1988

数据来源: WILEY

摘要:

AbstractBasal Cell Nevus Syndrome (BCNS) is a rare autosomal‐dominant inherited disorder associated with a marked hypersusceptibility to spontaneous and radiation‐induced skin cancer. We examined the changes in cell survival, unscheduled DNA synthesis (UDS) and the frequency of sister chromatid exchanges (SCE) induced by ultraviolet light (UVL) in confluent normal and BCNS fibroblasts. BCNS cells appeared slightly hypersensitive to the cytotoxic effects of UVL. The rate of UDS induced by UVL exposure in normal cell strains increased linearly following doses up to 30 J/m2, whereas in BCNS cells UDS became saturated at doses of 10 J/m2showing no further increase with doses up to 30 J/m2. UDS activity persisted for longer periods after UVL exposure in BCNS as compared with normal cells. The dose‐response relationship for UVL‐induced SCE was similar in normal and BCNS fibroblasts. However, the frequencies of UVL‐induced SCE declined to near background levels in normal cells following 12–24 hr of confluent holding prior to subculture whereas they remained elevated in BCNS cells with holding times up to 24 hr after UVL exposure. Overall, these results suggest that BCNS fibroblasts may have a diminished capacity for the repair of some type of DNA damage as compared with normal

ISSN:0270-3211    

DOI:10.1002/tcm.1770080104

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

年代:1988

数据来源: WILEY

摘要:

AbstractA homemade rust‐proof cutting fluid (RPCF) used in China was tested for carcinogenicity by an in vivo chronic experiment and for mutagenicity by the AmesSalmonellamicrosomal assay. Undiluted and threefold water‐diluted fluid were given as drinking water to groups of young adult Wistar rats for 2 years. The treatment induced 11/40 malignant tumors with 9/40 acinar adenocarcinomas of the pancreas in the high‐dose group. Simultaneous administration of ascorbic acid dissolved in the undiluted fluid at 2 g acid per 1 g sodium nitrite resulted in 1/40 pancreatic carcinoma. The results of the Ames test showed that the technical RPCF was mutagenic to TA100 with or without metabolic activation. It was concluded that the homemade RPCF, which is comprised of sodium nitrite, triethanolamine, and polyethylene glycol, may form direct‐acting mutagen(s) upon storage and form, in vivo, e.g., nitrosamines that caused acinar pancreatic carcinoma in Wistar rats. Simultaneous administration of ascorbic acid is suggested for the protection of workers exposed to the rust‐proof cutt

ISSN:0270-3211    

DOI:10.1002/tcm.1770080105

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

年代:1988

数据来源: WILEY

摘要:

AbstractColcemid is known to inhibit the spindle formation and to induce polyploidy and chromosomal nondisjunction. Using a V79 Chinese hamster cell line, we have shown that colcemid is able to induce the formation of cells that are numerically diploid but whose karyotype, when analyzed with the G‐banding technique, differs from that of the untreated ones. Even though these cells have a normal chromosomal constitution, they carry alterations in the chromosomal balance and, consequently, in gene dosage. This could result in an abnormal expression of cellular genes or in the expression of new or preexisting recessive mutations, even in a diploid chromosomal constitutio

ISSN:0270-3211    

DOI:10.1002/tcm.1770080106

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe induction of dominant lethal mutation in germ cells is the cause of embryonic death resulting in the reduction of litter size in the F1progeny. Dominant lethal mutations were induced when male mice were infected with live A2influenza virus. The chromosomal aberrations induced in the germ cells were shown to be responsible for the dominant lethality. Killed influenza virus was also potent in inducing chromosomal aberrations in spermatocytes of mice. In light of these observations, the UV‐inactivated virus was tested for its potency in induction of dominant lethality in both female and male germ cells. The virus‐inoculated females were mated with uninjected males and vice versa. Both the inactivated and live virus were found to induce dominant lethality in both female and male mice, indicating that not only the live virus but also the inactivated virus is capable of bringing about chromosomal damage resulting in dominant lethal

ISSN:0270-3211    

DOI:10.1002/tcm.1770080107

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

年代:1988

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770080108

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

年代:1988

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770080101

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

年代:1988

数据来源: WILEY