1,3,5-Trialkyl-2,4,6-triiodobenzenes: novel X-ray contrast agents for gastrointestinal imaging.

Examination of the gastrointestinal (GI) tract has been performed for decades using barium sulfate. Although this agent has many recognized limitations including extreme radiopacity, poor intrinsic affinity for the GI mucosa, and very high density, no alternative contrast agents have emerged which produce comparable or better contrast visualization. In fact, the various techniques of the GI radiologic examination (i.

The reproductive toxicology of intravenously administered MnDPDP in the rat and rabbit.

Purpose: The reproductive toxicology of mangafodipir trisodium (MnDPDP, Teslascan), a new hepatobiliary MR contrast agent, was evaluated in rats and rabbits.

Material And Methods: Male and female fertility and post-natal development were examined in rats after repeated i.v.

Developmental toxicity study of mangafodipir trisodium injection (MnDPDP) in New Zealand white rabbits.

Mangafodipir trisodium injection (MnDPDP) is an intravenously administered manganese chelate undergoing clinical evaluation for magnetic resonance imaging contrast enhancement of the hepatobiliary system. The anticipated single clinical dose for adults is 5 micromol/kg body wt. MnDPDP, as well as the inorganic salt, MnCl2, was previously shown to induce a specific syndrome of skeletal abnormalities in rats.

Developmental toxicity of mangafodipir trisodium and manganese chloride in Sprague-Dawley rats.

Mangafodipir trisodium (MnDPDP) is a manganese chelate being developed as a contrast agent for magnetic resonance imaging of the hepatobiliary system. The intended clinical dose is 5 mumol/kg. The potential for MnDPDP to induce embryotoxicity and/or teratogenicity in Sprague-Dawley rats was investigated.

Preclinical pharmacokinetics and general toxicology of iodixanol.

To document the safety of iodixanol and to assess its pharmacokinetic properties, extensive tests have been performed. Iodixanol was rapidly excreted, mainly via the kidneys, with a plasma half-life in rats and monkeys of 25 and 76 mins, respectively. The pharmacokinetic data were consistent with an extracelleular distribution of iodixanol.

Neural tolerability of iodixanol in mice and dogs after single and repeated intracisternal administration.

The neural tolerability of iodixanol has been assessed in studies in mice and dogs. The animals received up to 4 injections in the cisterna cerebellomedullaris while under light anesthesia. Iotrolan was included as a reference study in 1 study.

Evaluation of the potential of riddelliine to induce unscheduled DNA synthesis, S-phase synthesis, or micronuclei following in vivo treatment with multiple doses.

Riddelliine (RID) is a pyrrolizidine alkaloid found in plants of the genera Crotalaria, Amsinckia, and Senecio in the United States. RID has been extensively studied in a wide variety of in vitro short-term genotoxicity tests and has yielded positive responses in most test systems; however, there are fewer data available on the effects of RID in in vivo assays and no data under repeat-dose regimens. We have evaluated the ability of RID to induce unscheduled DNA synthesis (UDS) in hepatocytes, S-phase synthesis (SPS) in hepatocytes, and micronuclei in bone marrow from animals dosed for 5 or 30 days in conjunction with prechronic toxicity testing conducted for the National Toxicology Program.

Chromosome analysis of small and large L5178Y mouse lymphoma cell colonies: comparison of trifluorothymidine-resistant and unselected cell colonies from mutagen-treated and control cultures.

Mutagenesis assays at the thymidine kinase (TK) locus in L5178Y mouse lymphoma cells frequently yield mutant colonies with a bimodal size distribution. The objectives of this study were to determine whether a relationship exists between mutant colony size and chromosomal aberrations and whether the colony-size distributions obtained from this assay can indicate the clastogenic activity of a test chemical. Cells from 8 different types of L5178Y mouse lymphoma cell colonies were examined for chromosomal abnormalities within 10 cell generations after colony isolation.

Activity of 1,1,1- and 1,1,3-trichloroacetones in a chromosomal aberration assay in CHO cells and the micronucleus and spermhead abnormality assays in mice.

1,1,1- and 1,1,3-trichloroacetones (TCA) result from the disinfection of municipal water supplies with chlorine, and are direct-acting mutagens in the Ames/Salmonella assay. The objective of this study was to further investigate the genotoxicity of these compounds in mammalian cells using an in vitro chromosomal aberration assay in Chinese hamster ovary (CHO) cells and the micronucleus and spermhead abnormality assays in mice. Both compounds induced significant increases in structural chromosomal aberrations in CHO cells in the presence and in the absence of rat S9 metabolic activation (MA).

Mutagenic and clastogenic properties of 3-chloro-4-(dichloromethyl)-5-hydroxy-2 (5H)-furanone: a potent bacterial mutagen in drinking water.

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was found to be a direct-acting mutagen in the Ames test for strains TA1535, TA1538, TA92, TA97, TA98, TA100 and TA102. The highest mutagenic response (approximately 13,000 revertants/nmol) was seen in strain TA100. The TA100 response was six- to tenfold higher than in TA98, TA97, and TA102, and 100- to 500-fold higher than in TA1535, TA92, and TA1538.

Stable dicentric chromosomes induced by chemical mutagens in L5178Y mouse lymphoma cells.

Stable, tandem dicentric chromosomes were discovered in two mutant cell colonies resulting from exposure of L5178Y mouse lymphoma cells to chemical mutagens. These unusual dicentrics were present in all metaphase cells examined from these colonies, even after approximately 65 cell generations in culture. Observation of cells in metaphase and anaphase suggests that the interstitial centromere in these dicentrics is non-functional, and that the terminal centromere is solely responsible for their orderly anaphase segregation.

Chromosome analysis of trifluorothymidine-resistant L5178Y mouse lymphoma cell colonies.

Cells from small (sigma) and large (lambda) trifluorothymidine-resistant (TFTr) colonies induced by chemical mutagen treatment of TK+/-L5178Y mouse lymphoma cells were examined for chromosomal abnormalities. Analysis of G-banded metaphase chromosomes from 34 sigma-TFTr colonies revealed that cells from 20 (59%) possessed one or more chromosomal abnormalities. The most frequent (16/20 colonies) abnormality observed in cells from sigma-TFTr colonies involved the addition of extra chromatin to the distal region of one chromosome number 11.

Potential indicators of reproductive toxicity: testicular sperm production and epididymal sperm number, transit time, and motility in Fischer 344 rats.

Comprehensive assessment of the effects of chemicals on male reproductive functioning requires study of effects on spermatogenesis and the quality of spermatozoa produced. As potential indicators of toxic effects, we have examined sperm production rate (SPR) and epididymal sperm numbers, transit time, and motility (percentage motile cells and swimming speeds) in Fischer-344 (F-344) rats. Groups (n = 14 or 15) of rats at 6, 8, 10, 15, and 20 weeks of age were studied to investigate the suitability of these indicators for detecting toxic effects, and to establish the age at which this strain of rat sexually matures.

Sister-chromatid exchange and cell replication kinetics in fetal and maternal cells after treatment with chemical teratogens.

Effects of selected chemical teratogens on sister-chromatid exchange (SCE) frequencies and cell replication kinetics (CRK) in pregnant mice and their fetuses were investigated. Maternal and fetal cells were analyzed for SCE and classified as to whether they had gone through 1 (M1), 2 (M2), or 3 or more (M3+) cell cycles for quantifying cell replication kinetics and estimating average generation time (AGT). The teratogens tested in this system were mitomycin C (MMC), cyclophosphamide (CP), ethylnitrosourea (ENU), dimethylnitrosamine (DMN), lead acetate (LA), benzene (BEN), diethylstilbestrol (DES), diphenyldantoin (DPH), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and dimethyl sulfoxide (DMSO).

The biology of human male reproduction: an overview.

In this overview, the focus is on the biology of human male reproduction. The structure and function of the testis are described, and the endocrine control of spermatogenesis is discussed. The formation of spermatozoa during spermatogenesis and their maturation in the epididymis are reviewed.

Instability of nuclear chromatin in the ejaculated spermatozoa of fertile men.

In the present study of 15 fertile men, a mean of 89 +/- 3% of ejaculated cells had nuclei which were stable after treatment with 1% sodium dodecyl sulphate (SDS). Examination of repeated ejaculates demonstrated the constancy of the response of ejaculated spermatozoa from different men to SDS treatment. After 5 cycles of washing, the percentages of cells with stable nuclei after SDS treatment declined from 85 +/- 3 to 46 +/- 6% and ranged from 12 to 66% for different men.

Testicular sperm reserves in cockerels bearing Z-autosome translocations.

A technique of testicular homogenization and hemocytometric enumeration of elongated spermatids was applied to cockerels bearing Z-autosome translocations to estimate the effects of the translocations on sperm production. Testis weights, numbers of spermatids per gram of testis, and total number of spermatids were not significantly different between translocation-bearing cockerels and those of normal karyotype. In contrast to the adverse effects of X-autosome translocations on mammalian spermatogenesis, these data indicate that Z-autosome translocations do not quantitatively affect sperm production in cockerels.

Simultaneous assessment of human sperm motility and morphology by videomicrography.

Videotapes were analyzed to assess sperm motility and morphology in the semen of 5 fertile donors and 20 infertile patients. The slow motion playback control of the video recorder allowed simultaneous assessment of the motility and morphology of individual sperm cells. Similar values were obtained with this method for abnormal morphology more often were immotile or weakly motile than were the normal sperm in the same ejaculates.

Gonosome-autosome translocations in fowl: meiotic configurations and chiasma counts from singly and doubly heterozygous cockerels.

Many X-ray or chemical mutagen-induced chromosome translocations in domestic fowl (Gallus domesticus) are thought to involve microchromosomes as centromere donors to acentric macrochromosomal fragments. In order to study the involvement of microchromosomes in such translocations, and to investigate the possibility that such translocations are reciprocal, meiotic chromosomes from cockerels singly or doubly heterozygous for two different Z-autosome translocations were analyzed. Ring multivalents were observed in 74.

A Robertsonian translocation and its effect upon fertility in Brown Swiss cattle.

Metaphase chromosomes derived from leukocyte cultures of peripheral blood were observed in 299 head of Brown Swiss cattle. A Robertsonian translocation (centric fusion) was found in 31 of the animals. Estimated from this small sample 2.

Chromosomal analysis of fertile female heterosexual twins in cattle.

Metaphase chromosomes derived from leukocyte cultures of peripheral blood were examined in 15 fertile, female, heterosexual bovine twins. Of the 15 animals, 14 contained only XX cells in cultured leukocytes while the remaining female was chimeric containing 26% XY cells. The fertile, female, bovine, heterosexual twin demonstrating XX/XY sex chromosome chimerism in cultured leukocytes supplies evidence that chorionic fusion and vascular anastomosis may occur between male and female cattle twins without production of a freemartin.