摘要:

AbstractPrevious studies have shown that a new antischistosomal drug, 4‐isothiocyano‐4′‐nitro diphenylamine (CGP 4540, amoscanate), is not mutagenic in vitro, but the urines of animals treated with this drug have mutagenic activity. Mutagenicity can be eliminated by coadministration of some antibacterial agents and is not demonstrable in germ‐free animals. The present study describes attempts to isolate and identify intestinal microorganisms responsible for the mutagenic activation of amoscanate. Streptococcus equinus, isolated from the intestinal tract of mice, as well as some other species of Streptococcus, were found to produce mutagenic activation of amoscanate when introduced into animals pretreated with antibacterial agents. Similarly, incubation of these strains with amoscanate in vitro resulted in the formation of a mutageni

ISSN:0270-3211    

DOI:10.1002/tcm.1770010202

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

年代:1981

数据来源: WILEY

摘要:

AbstractVarious concentrations (1%, 10%, 50%, and 100%) of laboratory grade dimethylsulfoxide (DMSO) were administered by intraperitoneal injection to male Sprague‐Dawley rats for five consecutive days. Femoral bone marrow cells were harvested 24 hours after the last injection and were analyzed for cytogenetic aberration frequencies including chromosome breaks, chromatid breaks, markers, and severely damaged cells. Chromosome breaks revealed no differences between treated and control groups. Chromatid breaks were significantly elevated over the controls in all treated groups except at the 10% level. The incidence of markers was significantly elevated when compared to the controls in all treated groups. Only the high‐level (100%) group showed a significant increase in the incidence of severely damaged cells. When the above data were combined, the resultant percent of aberrant cells per animal was found to increase from 10% aberrant cells at the 1% DMSO level to 68.67% aberrant cells at the 100% DMSO level. The incidences of aberrant cells in all treated groups were significantly elevated when compared to the control (4% aberrant cells) group. These observations suggest that DMSO effectively disrupts the integrity of rat chromsome structure, and further investigation of the genetic activity of DMSO is warran

ISSN:0270-3211    

DOI:10.1002/tcm.1770010203

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe frequency of x‐ray‐induced chromosome aberrations in G0human lymphocytes was greatly increased when cells were incubated with cytosine arabinoside (ara‐C) after irradiation. The frequency of dicentrics increased with increasing ara‐C incubation times (one, two, and three hours). Lymphocytes from Down syndrome individuals were more sensitive to aberration induction by x‐rays in G0, and the increase in dicentric frequency with ara‐C incubation was much more rapid than with normal cells. When G2normal lymphocytes were x‐irradiated and incubated for two or three hours with ara‐C until fixation, there was a large increase in deletion frequency compared to cells x‐irradiated and incubated in the absence of ara‐C. However, no exchanges were observed in the presence of ara‐C, compared to 0.29 per cell as when x‐rays alone were given. These results form the basis for a discussion of the mechanism of aberration induction by x‐rays.Experiments with two chemicals, 4‐nitroquinoline‐N‐oxide and methyl methanesulfonate, show that chromosome‐type aberrations can be induced in G1treated lymphocytes incubated with ara‐C. However, these chemicals, in the absence of ara‐C incubation, induced no aberrations in G1at the concentrations used. The mechanism of aberration induction is discussed, particularly in terms of whether or not chemical

ISSN:0270-3211    

DOI:10.1002/tcm.1770010204

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

年代:1981

数据来源: WILEY

摘要:

AbstractInactivation of the infectivity of human cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV‐1) and type 2 (HSV‐2) has been observed following exposure to 4‐nitroquinoline 1‐oxide (NQO) or its metabolite, 4‐hydroxyaminoquinoline 1‐oxide (HAQO). The present study of the specificity of the chemical structure of 4‐nitroquinolines demonstrated that both the 4‐nitro and 1‐oxide groups were required for inactivation of virus infectivity. Reduction of the 4‐nitro group to a 4‐hydroxyamino group enhanced activity, while further reduction to an amino group resulted in loss of activity against virus infectivity. The capacity to inactivate virus was also lost by substitution of the pyridine ring for the quinoline nucleus of NQO. The relationship between the chemical structure and the ability to inactivate viruses studied here correlates well with earlier in vivo carcinogenicity studies of the sa

ISSN:0270-3211    

DOI:10.1002/tcm.1770010205

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

年代:1981

数据来源: WILEY

摘要:

AbstractThirty‐two diploid fibroblast strains from individuals with the three forms of retinoblastoma were examined with an in vitro clonogenic survival assay to determine their sensitivity to killing by X rays. Strains from sporadic unilateral retinoblastoma patients and normal controls were indistinguishable from one another (group D0's = 147 ± 15 rads and 146 ± 5 rads, respectively) while the strains from patients with the hereditary form of the disease were significantly more X‐ray sensitive (D0= 111 ± 12). Strains derived from individuals with the D‐deletion form of the disease resembled the hereditary strains with respect to sensitivity and heterogeneity, suggesting a possible, common etiology for these two forms of the disease.A DNA‐repair defect is hypothesized as reflected by the observed hypersensitivity to X‐irradiation in these cells. We suggest that this defect may be associated with the enhanced frequency of spontaneous and radiationinduced second tumors seen in some retinoblast

ISSN:0270-3211    

DOI:10.1002/tcm.1770010206

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

年代:1981

数据来源: WILEY

摘要:

AbstractForelimbs of mouse fetuses were examined for tissue‐specific, drug‐induced alterations in their biochemical composition. The activity of the enzyme creatine phosphokinase (CPK; to estimate myogenesis) and the content of hydroxyproline (HP; to estimate chondrogenesis) were compared in homogenates of control and treated mouse‐fetus forelimbs on day 14 of gestation. In addition, the content of DNA, RNA, and protein was also measured. Injection of 6‐aminonicotinamide (6‐AN) (15 mg/kg) on day 10 resulted in an overall growth retardation in day 14 fetuses and all biochemical parameters tested were reduced. The ratio of HP:CPK was unaffected by 6‐AN treatment. Retinoic acid (vitamin A acid; 100 mg/kg), administered to pregnant female mice on day 10, produced severe forelimb defects and resulted in a significant reduction in day 14 forelimb HP and RNA content, without altering CPK, DNA, or protein; thus, the HP:CPK ratio was decreased. These results indicated that (1) 6‐AN nonspecifically retards growth and cytodifferentiation in limbs; (2) retinoic acid inhibits synthesis of collagen and RNA; (3) retinoic acid has a differential effect upon chondrogenic and myogenic tissues of the limb, and (4) the comparison of HP content and CPK activity in tissue homogenates is an acceptable method of evaluating teratogenic compounds for sele

ISSN:0270-3211    

DOI:10.1002/tcm.1770010207

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe YFF sperm assay, which is a quantification of the incidence of sperm with two fluorescent bodies (YFF = two fluorescent bodies), was performed to measure Y chromosomal nondisjunction. Three categories of human sub‐ jects were analyzed: (1) nonexposed, (2) exposed to antineoplastic agents ‐ ie, chemo‐ and radiation therapy, and (3) dibromochloropropane (DBCP)‐exposed. The nonexposed individuals demonstrated a relatively constant mean YFF value of 1.3%, which was consistent with historical controls in this laboratory and with the results of other investigators. Further, a one‐way analysis of variance among the means of the control samples revealed no statistical differ‐ ences either between these men or within each man's samples. The individuals exposed to antineoplastic agents showed a three‐ to four‐fold increase in the incidence of YFF sperm three to six weeks after the initiation of exposure to Adriamycin® and X‐irradiation. The maximum percentages of YFF per 1,000 sperm for each individual in this exposed group were analyzed by Wilcoxon's distribution free rank sum test using a one‐sided alternative. The exposed individuals' maximum YFF percentages were statistically significantly increased when compared to the maximum YFF values of the non‐ exposed controls. The individuals exposed to the nematocide DBCP also exhibited a statistically significant increase in the number of sperm con‐ taining two Y chromosomes as determined by chi‐square analysis with one degree of freedom (P<0.01).Data presented herein show statistically significant increases in the incidence of double Y chromosomes as measured by the presence of YFF sperm following exposure to Adriamycin®, X‐irradiation, and DBCP. It is suggested that men who have a history of antineoplastic therapy could be evaluated for evidence of Y‐Y nondisjunction with this method. In the event of an increased YFF sperm level, genetic counseling and amniocentesis should be made available to the spouse where pregnancy has occurred. Further, be‐ cause this procedure measures gametic mutation, is relatively simple, and is noninvasive, it should be considered for inclusion as part of a battery of medical tests for

ISSN:0270-3211    

DOI:10.1002/tcm.1770010208

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe carcinogenicity of quercetin, a flavonol, was tested in six‐week‐old ddY mice of both sexes. Groups of 38 males and 35 females were given pellet diet containing 2% quercetin throughout their life span. As controls, 16 males and 15 females were given basal diet. Animals in both test and control groups developed leukemia and tumors of the lung, forestomach, mammary gland, adrenal, and soft part tissues. In addition, some animals in groups treated with quercetin developed tumors of the heart, liver, salivary gland, ovary, and uterus. The incidences of these tumors in test and control groups were not statistically differ

ISSN:0270-3211    

DOI:10.1002/tcm.1770010209

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

年代:1981

数据来源: WILEY

摘要:

AbstractNickel carbonyl was administered to groups of pregnant hamsters by inhalation (0.06 mg Ni(CO)4/liter/15 min) on days 4, 5, 6, 7, or 8 of gestation. The dams were killed on day 15 of gestation, and the fetuses were examined for malformations. Exposure to Ni(CO)4on days 4 or 5 of gestation resulted in malformations in 5.5% (8/146) and 5.8% (10/171) of the progeny, respectively (P<0.05, versus 0/95 in controls). The proportions of litters with malformed fetuses were 33% (4/12) and 24% (4/17) in dams exposed to Ni(CO)4on days 4 and 5 of gestation (P<0.05, versus 0/9 in litters of control dams). Progeny of dams exposed to Ni(CO)4on days 4 and 5 included 9 fetuses with cystic lungs, 7 fetuses with exencephaly, 1 fetus with exencephaly plus fused rib, and 1 fetus with anophthalmia plus cleft palate. Hemorrhages into serous cavities were found in 18% (26/146) and 25% (42/171) of fetuses of dams exposed to Ni(CO)4on days 4 or 5 of gestation. Such hemorrhages were not observed in controls. In progeny of dams exposed to Ni(CO)4on days 6 or 7 of gestation, there was 1 fetus with fused ribs and there were 2 fetuses with hydronephrosis. In another experiment, pregnant hamsters were exposed to inhalation of Ni(CO)4(0.06 mg/liter/15 min) on day 5 of gestation; these dams were permitted to deliver their litters and to nurse their pups. On the day of delivery, there was no significant difference in the average number of live pups in the Ni(CO)4‐exposed litters compared to control litters. Neonatal mortality was increased in Ni(CO)4‐exposed litters; by day 4 postpartum, the number of live pups averaged 7.6 ± 1.5 in Ni(CO)4‐exposed litters (P<0.01 versus 9.6 ± 1.8 pups in control litters). This study demonstrates that Ni(CO)4is teratogenic and embryotoxic in Syrian h

ISSN:0270-3211    

DOI:10.1002/tcm.1770010210

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

年代:1981

数据来源: WILEY

摘要:

AbstractUrine was collected from Sprague‐Dawley rats injected intraperitoneally with a suspension of 2‐acetylaminofluorene (AAF) or with an inert suspension vehicle. Morphological transformation was observed in clonal cultures of secondary passage hamster embryo cells (HEC) after the addition of AAF‐treated rat urine or concentrated urine extracts prepared by incubating the urine with β‐glucuronidase. No morphological alteration was observed in cultures treated with urine (or urine extracts) from rats injected with the suspension vehicle alone. The presence of N‐hydroxy‐ and ring‐hydroxylated metabolites of AAF in the AAF‐treated concentrated urine extract was confirmed by highperformance liquid chrom

ISSN:0270-3211    

DOI:10.1002/tcm.1770010211

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

年代:1981

数据来源: WILEY