bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of rat lymphocyte activation of benzo[a]pyrene, 2‐acetylaminofluorene, and several of their metabolites to mutagenic and DNA‐damaging species in vitro
Authors: Gao Ning , Aidoo Anane , Heflich Robert H. 
Published: February 2006

AbstractRat lymphocytes are a potentially useful and convenient cell system for monitoring the genotoxic effects of chemicals in vivo, but little is known about the ability of these cells to metabolize promutagens to genotoxic species. In this study, Fischer 344 rat lymphocytes were treated in vitro with benzo[a]pyrene (BaP), 2‐acetylaminofluorene (2‐AAF), and several of their metabolites, and DNA damage was measured using nucleoid sedimentation analysis. Of the BaP derivatives, BaP 4,5‐oxide and BaP 7,8‐diol‐9,10‐epoxide decreased lymphocyte nucleoid sedimentation, whereas BaP and BaP 7,8‐dihydrodiol had little effect. Among the 2‐AAF derivatives, N‐acetoxy‐2‐AAF, N‐hydroxy‐2‐AAF, and N‐hydroxy‐2‐aminofluorene damaged rat lymphocyte nucleoids, whereas 2‐AAF, 2‐aminofluorene, and fluorene produced little detectable damage. The decrease in nucleoid sedimentation produced by N‐hydroxy‐2‐AAF was not inhibited by paraoxon, salicylamide, or 2‐aminofluorene, whereas paraoxon inhibited damage produced by N‐acetoxy‐2‐AAF. In co‐culture assays, rat lymphocytes increased the mutagenicity of N‐hydroxy‐2‐AAF in Salmonella typhimurium strain TA98, but mediated little or no mutagenic response with BaP, BaP 7,8‐dihydrodiol, and 2‐AAF. Also, human lymphocytes, but not rat lymphocytes, mediated a positive mutagenic response with BaP 7,8‐dihydrodiol in Chinese hamster ovary UV5 cells. Although rat lymphocytes may metabolize certain proximal genotoxic chemicals to DNA‐damaging species (e.g., N‐hydroxy‐2‐AAF), these data suggest that in vivo lymphocyte DNA damage is more likely to result from lymphocytes encountering reactive chemical derivatives produced by other cells. It is also clear that differences exist between the ability of human and rat lymphocytes to activate promutagens, and this may impact on the use of the rat model to predict the genotoxicity of chemicals in humans.
In vitro reduction of peroxidation in UVC‐irradiated cell cultures by concurrent exposure with Bowman‐Birk protease inhibitor
Authors: Baturay Nesrine Z. , Roque Henry 
Published: February 2006

AbstractBowman‐Birk protease inhibitor (BBI), extracted from soybean flour, has been shown to protect cells from damage after UVC irradiation. BBI also reduces the number of transformed foci following exposure to the same doses of UVC irradiation. Proteins have been reported to act as antioxidants by their sheer intracellular bulk. In this study we assessed BBI's ability to attenuate UVC‐irradiation‐induced peroxidation.Balb c/3T3 cells, clone A31, subcloned by this laboratory were used. Treatment groups consisted of cells suspended in Hanks' Balanced Salt Solution with and without 100 μg/ml of a crude soybean extract containing the Bowman‐Birk protease inhibitor. Cells were exposed to irradiation in suspension by using GE (G8T5) germicidal lamps which deliver predominantly 254 nm light at 0.385 J/m2/s as measured at the cell surface. Aliquots of UVC‐exposed cells were homogenized in HBSS in the presence and absence of 100 μg/ml BBI with a motor‐driven Teflon pestle and assayed for peroxidation.The results showed significant (P < 0.0001) protection afforded by BBI against peroxidation at 1.16 (65%), 1.93 (60%, and 2.70 (48%) J/m2 of UVC irradiation. Transformation was reduced to 0.33 foci per dish at all levels of radiation exposure.
An appreciation of the maximum tolerated dose: An inadequately precise decision point in designing a carcinogenesis bioassay?
Authors: Clayson David B. , Iverson Frank , Mueller Rudolf 
Published: February 2006

AbstractCancers arise in specific tissues. One difficulty with the present definitions of the Maximum Tolerated Dose (MTD), as they pertain to the rodent cancer bioassay, is that they base MTD on relatively crude parameters associated with the well‐being of the entire animal rather than with the lack of specific tissue toxicity. Additional factors that could be included in the MTD definition, or could be separately determined, are addressed. Many of these factors refer to toxic behavior in one or a few tissues and, if used in setting the MTD, may mask more relevant events occurring at higher dose levels in other tissues. Reducing the MTD to a level that fails to take into account pesticide or drug‐related toxicity may lead to the loss of relevant information in the bioassay. It is concluded, therefore, that there are two possible approaches to a more appropriate use of the MTD. The highest dose of the test agent (MTD) may be chosen (i) to lie below the thresholds of carcinogenicity‐related non‐genotoxic toxicity or (ii) the present high level MTD may continue to be used and tumors that arise may be classified as being irrelvant to humans at some or all exposure levels. The latter approach is to be preferred. It has the potential to avoid missing high level effects of the test agent that may be relevant to the human population. © 1992 Wiley‐Liss, Inc.
Diphenylhydantoin is not genotoxic in a battery of short‐term cytogenetic assays
Authors: Kindig D. , Garriott M. L. , Parton J. W. , Brunny J. D. , Beyers J. E. 
Published: February 2006

Abstract5,5‐Diphenylhydantoin (DPH) is an antiepileptic drug associated with an increase in malformations in infants born to women taking DPH during pregnancy. Positive and negative results have been reported by various investigators for in vivo and in vitro chromosome aberration (CAB) assays, in vivo and in vitro sister chromatid exchange (SCE) assays, and in vivo micronucleus tests (MNT). In this laboratory, DPH was tested in an in vitro CAB assay using Chinese hamster ovary cells with and wihout an S‐9 activation system, an in vivo SCE assay in female CD‐1 mice, an in vivo MNT, using both male and female CD‐1 mice, and a transplacental micronucleus test. The results from this comprehensive battery of cytogenetic tests were uniformly negative and support a conclusion that the known teratogen, DPH, is not clastogenic. © 1992 Wiley‐Liss, Inc.
Effects of reproductive tract glutathione enhancement and depletion on ethyl methanesulfonate‐induced dominant lethal mutations in Sprague‐Dawley rats
Authors: Gandy J. , Bates H. K. , Conder L. A. , Harbison R. D. 
Published: February 2006

AbstractThe effects of altering glutathione (GSH) levels in the male reproductive tract have been studied in an attempt to establish a link between chemical‐induced perturbations in glutathione and susceptibility of spermatozoa to chemical insult. Tissue GSH levels were enhanced by a treatment regimen of N‐acetylcysteine (NAC) (250 mg/kg, 4 treatments at 2 h intervals). With this treatment, GSH levels in liver, testis, caput epididymis, and cauda epididymis were elevated to 126%, 110%, 178%, and 136% of control values. Sexually mature male rats were then treated with NAC and challenged with a dose of EMS (100 mg/kg) to determine if enhanced tissue GSH would protect against EMS‐in‐duced dominant lethal mutations. Pretreatment with NAC significantly decreased the post‐implantation loss from 7.05 ± 0.57 with EMS alone to 5.28 ± 0.47. Conversely, a dominant lethal assay was conducted using different doses of phorone pretreatment to determine the relative contribution of hepatic versus reproductive tract GSH in protecting against EMS‐induced dominant lethal resorptions. Doses of 100 mg/kg and 250 mg/kg phorone significantly lowered both hepatic and reproductive tract GSH while 25 mg/kg lowered only hepatic GSH. These three dose levels were used as pretreatments in a dominant lethal study followed by a challenge administration of EMS (50 mg/kg), which is a threshold dose of EMS for producing dominant lethal mutations. Comparison against controls demonstrated a significant potentiation of fetal resorptions in all groups receiving phorone pretreatment, including the 25 mg/kg pretreatment group which only lowered hepatic GSH prior to EMS challenge. The results of these experiments indicate that GHS reserve in the male reproductive tract are insufficient to protect developing spermatozoa from damage by alkylating agents in the absence of hepatic GSH. © 1992 Wiley‐Liss, Inc.
Lack of synergism among DMAB, BOP, and MNU in induction of carcinomas of the rat ventral prostate
Authors: Shirai Tomoyuki , Yamamoto Atsushi , Imaida Katsumi , Tamano Seiko , Mori Toshio , Hasegawa Ryohei 
Published: February 2006

AbstractThe present experiment was undertaken to investigate possible synergism in induction of rat prostate tumor. F344 rats were repeatedly administered the prostate carcinogens 3,2′ ‐dimethyl‐4‐aminobiphenyl (DMAB), N‐nitrosobis(2‐oxopropyl)amine(BOP), and N‐methylnitrosourea (MNU) sequentially or together at times of hormonal castration induced regenerative cell proliferation of prostate epithelial cells. Group 1 animals received two 100 mg/kg doses of DMAB, two 20 mg/kg applications of BOP, and two times 15 mg/kg of MNU. Groups 2,3, and 4, respectively, received each of the carcinogen treatment alone. Group 5 was given 6 applications of all three in combination, each at one‐third the dose administered to the other groups. The results showed a clear synergism in enhanced tumor development in the colon but not in the prostate, in which the incidence of lesions induced by the three carcinogens was similar to that with DMAB alone. © 1992 Wiley‐Liss, Inc.
Identification of kinetochores and DNA synthesis in micronuclei induced by mitomycin C and colchicine in chinese hamster ovary cells
Authors: Majone Franca , Tonetto Sabina , Soligo Carla , Panozzo Marina 
Published: February 2006

AbstractThe presence of kinetochore and DNA synthesis in micronuclei (MN) induced in Chinese hamster ovary (CHO) cells by clastogenic and aneuploidogenic substances such as mitomycin C (MMC) and colchicine was determined by immunofluorescence technique using CREST antikinetochore antibodies and anti‐bromodeoxyuridine (BrdUrd) antibodies. A cytofluorimetric analysis was also performed. Colchicine significantly increased micronucleated cells at least up to 96 h from the end of treatment. As expected, among colchicine‐induced micronucleated cells the majority contained at least one CREST + MN. MMC induced a significant increase in micronucleated cells up to 120 h from the end of treatment and the great majority of MN lacked kinetochore fluorescence, indicating that MMC‐induced MN were derived from acentric fragments. However, colchicine and MMC at 48 and 72 h from the end of treatment induced a significant increase of CREST— and CREST + MN, respectively, suggesting an induction of clastogenicity by colchicine and aneuploidy by MMC. The clastogenic effect of colchicine after 48 h was also confirmed by the presence of chromatid fragments in metaphase cells. A cytofluorimetric analysis indicated that, as aspected, colchicine and MMC interfere with the G2/M and S phases, respectively; however, a slight interference of colchicine with the S phase was also observed. DNA synthesis was present in MN and it was in most cases synchronous with synthesis in the main nucleus. The frequency of cells with MN in S phase observed in untreated or MMC‐treated cells is in agreement with the proportion of cells without MN showing DNA synthesis. On the contrary, the frequency of cells with MN in S phase observed in colchicine‐treated cells was significantly lower than that observed in control and MMC‐treated cells. © 1992 Wiley‐Liss, Inc.
Influence of periconceptional zinc deficiency on embryonic plasma membrane function in mice
Authors: Peters Jeffrey M. , Wiley Lynn M. , Zidenberg‐Cherr Sheri , Keen Carl L. 
Published: February 2006

AbstractPericonceptional Zn deprivation can affect development of 2‐ and 4‐cell mouse embryos in vitro as evidenced by fewer cells per embryo and delayed blastocyst development after 72 h in culture. One mechanism by which this could be occurring is through changes in oocyte and embryonic membrane structure/function. To test this idea, 3H‐glycine uptake was measured in unfertilized oocytes and preimplantation embryos recovered from mice fed control ( + Zn; 50 μg Zn/g diet) or low Zn ( − Zn; ⩽O.4 μg Zn/g diet) diets for 6 days. In a second experiment, we assessed the in vitro development of preimplantation embryos in medium designed to inhibit cavitation through changes in membrane‐associated sodium flux. Preimplantation embryos from − Zn and + Zn mice recovered on day 1 of gestation were cultured in medium containing 147.2 mM sodium (normal) or 123 mM sodium (low sodium) for 48 h. In experiment 1, glycine uptake was similar in embryos from + Zn and − Zn mice, suggesting that the impaired in vitro development of embryos from − Zn mice is not due to gross changes in sodium‐dependent cell membrane function. In experiment 2, embryos recovered from − Zn mice and cultured in normal sodium medium contained fewer cells than controls. Embryos from both groups cultured in low sodium medium contained fewer cells than their normal sodium controls; the percent difference in cell number was 50 ± 8% and 56 ± 11% for embryos from + Zn and − Zn mice, respectively. The lack of an exacerbation of Zn deficiency‐induced impairment of in vitro development with the low sodium challenge further supports the idea that the reduction in embryonic cell number is not due to gross alterations in membrane structure and/or function. ©1993 Wiley‐Liss, Inc.
Developmental toxicity and teratogenicity of trichosanthin, a ribosome‐inactivating protein, in mice
Authors: Chan W. Y. , Ng T. B. , Wu P. J. , Yeung H. W. 
Published: February 2006

AbstractThe embryotoxic and teratogenic effects of trichosanthin (TCS), a protein isolated from tubers of Trichosanthes kirilowii (family Cucurbitaceae), were studied both in vivo and in vitro. The protein was administered i.p. to ICR mice on day 8.0 of pregnancy, and the animals were sacrificed 1 day before parturition. The fetuses were fixed and subsequently sectioned. At the highest TCS dose employed (7.5 mg/kg body weight), the viability of fetuses declined to 70.2%, compared with 96.5% in the saline‐treated control group. The number of resorbed fetuses increased, and the crown‐rump length of the surviving fetuses was reduced. At the doses of 5.0 and 7.5 mg TCS/kg body weight, 2.3% and 9.0%, respectively, of the surviving fetuses were found to be abnormal. The abnormalities observed included exencephaly, micromelia, and short tail. When mouse embryos at the early organogenesis stage were cultured with TCS at a dose of 200 μg/ml or above, a significantly larger number of embryos were found to be abnormal as compared with the controls. The abnormalities were observed in the head, trunk, and limb regions. Hence, TCS produced adverse effects on prenatal development both in vivo and in vitro. ©1993 Wiley‐Liss, Inc.
Teratogenicity and carcinogenicity in a twin exposed in utero to cyclophosphamide
Authors: Zemlickis Donna , Lishner Michael , Erlich Robert , Koren Gideon 
Published: February 2006

AbstractA 29‐year‐old pregnant woman diagnosed with acute lymphocytic leukemia maintained remission with daily cyclophosphamide and intermittent prednisone treatment. She delivered a male twin with multiple congenital abnormalities who was diagnosed with papillary thyroid cancer at 11 years of age and stage III neuroblastoma at 14 years of age. The female twin was unaffected and has exhibited normal development to date. First trimester exposure to cylcophosphamide has been associated with major malformations. Metabolites of cyclophosphamide have been demonstrated to be teratogens and carcinogens in animals. Differences in placental or fetal hepatic cytochrome P‐450 may account for the variability in response between the twins. In addition, disparity between the twins may be the result of differences in metabolite inactivating enzymes present either in fetal liver or placenta. The risk of second malignancies caused by alkylating agents such as cyclophosphamide has been well documented in adults and children but to the best of our knowledge this is the first description of transplacental second cancer. ©1993 Wiley‐Liss, Inc.
Teratogenic effect of hyperthermia during early organogenesis period in mice
Authors: Hande M. Prakash , Veena K. 
Published: February 2006

AbstractPregnant Swiss albino mice were subjected to 41, 42, or 43°C temperature for 10 minutes on day 6.5 of gestation. Another group of animals treated at 37°C was used as control. All animals were killed on the 18th day of gestation and fetuses were examined for prenatal mortality, growth retardation, and microphthalmia incidence. Results indicated a dose dependent increase in the mortality rates with a 42% death in the 43°C group. Treatment with the higher temperatures (42 and 43°C) resulted in a significant increase in the number of growth retarded fetuses and in the incidence of microphthalmia. Reduction in head length and decrease in brain weight were observed in the group exposed to 43°C, particularly in the growth retarded fetuses. However, the percent brain weight(g)‐body weight(g) ratio did not show any significant difference from the control values. ©1993 Wiley‐Liss, Inc.
Interception of reactive, DNA adduct‐forming metabolites present in rodent serum following carcinogen exposure: Implications for use of body fluids in biomonitoring
Authors: Garg Achal , Beach Andrew C. , Gupta Ramesh C. 
Published: February 2006

AbstractThe detection of adduct‐forming metabolites in the serum of carcinogen treated animals by 32P‐postlabeling was evaluated as a novel approach to overcome the stringent requirement of obtaining DNA from tissues in human biomonitoring assessments. Benzo[a]pyrene (BP) was given i.p. to B6C3F1, C57B1/6, ICR, and DBA/2 mouse strains as well as Sprague‐Dawley rats. Three adducts related to BP were detected in the liver and/or lung of Sprague‐Dawley rats or B6C3F1), C57B1/6, and ICR mice; a single adduct was detected in the liver and lung of the DBA/2 mouse strain. Adducts chromatographically similar to those found in these tissues were also detected when salmon sperm DNA was incubated with the serum of BP‐treated animals. Benzidine treatment induced the formation of one adduct in the liver of B6C3F1 mice, which was chromatographically similar to dG‐C8‐N′‐acetylbenzidine. An identical adduct was detected in the salmon sperm DNA incubated with the serum of these mice. Cyclopenta[cd]pyrene treatment produced four major and three minor adducts in the liver or lung of B6C3F1 mice, all but two of which were detected in DNA incubated with serum of cyclopenta[cd]pyrene‐treated animals. Large interstrain differences in the serum level of BP adduct‐forming metabolites as well as tissue DNA adducts were found which correlated with previously observed strain‐specific trends in sensitivity to PAH‐mediated carcinogenesis. Thus, levels of BP adduct‐forming metabolites were found in the following descending order: B6C3F1, C57B1/6, ICR, and DBA/2. BP‐derived adduct‐forming metabolites were detectable as late as 2 d and 5 d post‐treatment in the serum of C57B1/6 mice or Sprague‐Dawley rats, respectively, which seems to coincide well with the reported species‐specific turnover of serum albumin; a protein know to be involved in the transport of reactive metabolites throughout the systemic circulation. The results obtained clearly indicate the presence of adduct‐forming carcinogen metabolites in the serum of treated animals, which seemingly irrespective of their chemical nature, can be intercepted with exogenous DNA and detected by 32P‐postlabeling. Successful application of a serumbased approach coupled with the use of the generally applicable, ultrasensitive 32P‐postlabeling assay could evade the need for obtaining DNA from tissues, currently the major impediment in human biomonitoring studies. ©1993 Wiley‐Liss, Inc.
Relationship between blood group‐A antigen expression and malignant potential in hamster pancreatic cancers
Authors: Hirota Masahiko , Egami Hiroshi , Mogaki Masatoshi , Kazakoff Katherine , Chaney William G. , Pour Parviz M. 
Published: February 2006

AbstractThe loss of expression of the ABH blood group antigens is suggested to be associated with more aggressive behavior of cancers. We have compared the growth behaviors of two hamster pancreatic cancer cell lines with different blood group‐Aexpressions. PC‐1.0 cells, which expressed blood group‐A antigen poorly, showed a faster growth in vitro and in vivo when implanted into the pancreas of homologous animals, whereas PC‐1.2 cells, all of which express the antigen, had a slower growth rate both in vitro and in vivo. PC‐1.0 also tended to metastasize, whereas PC‐1.2 cells grew primarily locally. The allografts of both PC‐1.2 cells (PC‐1.2AG) and PC‐1.0 cells (PC‐1.0AG) and the metastases of PC‐1.0 cells expressed blood group A antigen in a similar rate. There was no significant difference in the number of A‐antigen positive cells (A +) between the PC‐1.2AG and PC‐1.0AG, although the expression of A antigen in PC‐1.0AG showed a greater heterogeneity. The combined immunohistochemistry and autoradiography did not show any significant differences in the labeling index of A + or A− cells between the two allografts. Thus, the results indicate that blood group A antigen expression is unrelated to malignancy in this model. The faster growth rate of PC‐1.0 cells may be due to their shorter cell cycle. ©1993 Wiley‐Liss, Inc.
Time‐dependent differences in the development of somites of four different mouse strains
Authors: Thiel Renate , Chahoud Ibrahim , Jürgens Maike , Neubert Diether 
Published: February 2006

AbstractIn studies on reproductive toxicity and especially teratogenicity, animals are often treated at defined stages of pregnancy. As a result the exposure to a certain teratogen can lead to striking differences in the formation of abnormalities in different strains of the same species. As a contribution to the discussion about the reasons for these differences, we examined the somite development of four different strains of mice during organogenesis. The embryos of pregnant females of the inbred strains DBA/2J, BALB/cJ, and C57BL/6J and of the outbred strain Han:NMRI were studied on days 9, 10, 11, or 12 of gestation. As a criterion for development the somite pairs were evaluated on the respective days. There were remarkable differences in the somite number, even within one litter. The largest variation (minimum vs. maximum) was 14 pairs of somites. The regression curves did not exhibit major differences in the speed of somite development from day 9 to day 12 between the four strains. We have to conclude from our results that the individual embryonic stages within one litter may vary by nearly 1 day, and that there may be a delay of half a day in the embryonic development between different strains of mice. ©1993 Wiley‐Liss, Inc.