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PubMed1978

Construction of an Escherichia coli strain which excretes abnormally large amounts of adenosine 3',5'-cyclic monophosphate.

It has previously been shown that an Escherichia coli CRP- strain 5333 accumulates abnormally large amounts of adenosine 3',5'-cyclic monophosphate (cAMP). Using P1 transduction, the CRP- character was transferred to E. coli Crookes strain which is deficient for cAMP phophodiesterase (CPD-). The resulting strain HY22 (CRP-, CPD-) accumulates greater amounts of cAMP both intracellularly and extracellularly than does 5333. In glucose minimal medium, an HY22 cell accumulates 100 times more cAMP intracellularly and excretes cAMP 150 times faster than does a wild-type E. coli cell.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Vasopressin and atrial natriuretic peptide release in cardiopulmonary denervated dogs.

To assess the effect of cardiopulmonary denervation on the release of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP), either hemorrhage (1.0 ml.kg-1.min-1, for 40 min) or an infusion of 3% dextran in lactated Ringer solution (RL) (3% dextran in RL, 1.0 ml.kg-1.min-1, for 40 min) was carried out in chronic cardiopulmonary denervated (CPD, n = 7) and sham-operated (SO, n = 7) dogs under anesthesia. Plasma AVP increased significantly in both groups during hemorrhage, but its rise was significantly attenuated in CPD dogs. Plasma ANP decreased similarly during hemorrhage in both groups. An infusion of 3% dextran in RL decreased significantly plasma AVP during its whole period in SO dogs, but AVP release was only suppressed in the late period in SO dogs. Plasma ANP increased significantly during its infusion in both groups. These results indicate that cardiopulmonary denervation may attenuate the release of AVP in response to either hemorrhage or blood volume expansion but may not affect the release of ANP in response to the blood volume change. Moreover, a large increase in plasma ANP may attenuate the release of AVP.

Animals↗
PubMed1991

Fibroblasts of rabbit kidney in culture. I. Characterization and identification of cell-specific markers.

There is currently no information available as to whether different renal fibroblast subpopulation can be identified and whether they show differences in functional properties. We therefore compared the growth characteristics of interstitial fibroblasts derived from the rabbit renal cortex and inner medulla (papilla) and sought cell-specific markers for the two populations of cells. Analyses of the population dynamics revealed that the mitotic lifespan of papillary fibroblasts (PF) is approximately 50% longer than that of cortical fibroblasts (CF), with the former going through 20 cumulative population doublings (CPD) before transition into terminally differentiated postmitotic cells compared with 9 CPD in CF. PF and CF populations contained three types of mitotically active cells (MFI, MFII, MFIII) and three types of postmitotic cells (PMFIV, PMFV, PMFVI) differentiating along a terminal cell lineage from MFI through PMFVI. In both PF and CF cultures the percent of MF-type cells decreased and the percent of postmitotic cells increased with successive doublings. Two-dimensional polyacrylamide gel electrophoresis of uniform clonal populations of MFIII-type cells revealed two specific proteins for PF-MFIII-type cells, pf1 and pf2, and three specific proteins for CF-MFIII-type cells, cf1, cf2, and cf3. Additionally, a monoclonal antibody was raised that does not recognize CF in culture, but reacts strongly with PF. These studies demonstrate that rabbit renal PF have a pattern of growth in vitro that is distinct from that of CF and that they can be positively identified by specific immunological and protein markers in vitro.

Animals↗
PubMed1994

Spatiotemporal response properties of direction-selective neurons in the nucleus of the optic tract and dorsal terminal nucleus of the wallaby, Macropus eugenii.

1. The spatial and temporal response characteristics of direction-selective neurons in the nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT-DTN) of the wallaby were established using moving sinusoidal gratings. This is the first comprehensive investigation of the spatiotemporal response characteristics of NOT-DTN neurons in any species. 2. The analysis revealed two main classes of cells. The first class, referred to as slow neurons, are maximally sensitive to motion at low temporal frequencies (< 1 Hz) and high spatial frequencies (0.5-1.0 cpd). The second class, referred to as fast neurons, are most sensitive to motion at high temporal frequencies (> 10 Hz) and moderate to low spatial frequencies (0.1-0.5 cpd). The fast neurons also have a domain of high sensitivity at low temporal frequencies and high spatial frequencies. As the neurons are tuned to specific temporal frequencies of motion, rather than image velocities, it is suggested that the motion detectors are of the delay-and-compare type and code local motion-related changes in contrast or luminance. 3. Both classes of neuron are highly direction-selective in the midranges of their spatiotemporal tuning curves, i.e., the firing rates increase during motion in the preferred direction (temporonasal movement through the visual field of the contralateral eye) and decrease during motion in the opposite direction. At high temporal and low spatial frequencies, however, the slow neurons are inhibited by motion in both directions along their preferred axis. It is argued that this bidirectional inhibition at high speeds may act to inhibit ocular following during saccades and may act as a gain control mechanism preventing excessive overshoot in eye velocity at motion onset, when retinal-slip velocities are high. 4. The fast neurons probably have two functions. First, they are suited to initiating ocular following responses when image motion is quite fast. Second, their spatiotemporal tuning makes them candidates for supplying a velocity error signal into the velocity storage mechanism, which is most prominent at high stimulus speeds. 5. Fourier analysis of the peristimulus time histograms derived from the response of both the slow and fast neurons revealed that the main frequency components of the responses occurred at the fundamental and second harmonic frequencies of the input signal at low stimulus temporal frequencies (< 3.04 Hz). At higher stimulus frequencies, the responses contained significant frequency components at higher odd-harmonics of the input signal.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

Spatiotemporal properties of fast and slow neurons in the pretectal nucleus lentiformis mesencephali in pigeons.

Neurons in the pretectal nucleus lentiformis mesencephali (LM) are involved in the analysis of optic flow that results from self-motion. Previous studies have shown that LM neurons have large receptive fields in the contralateral eye, are excited in response to largefield stimuli moving in a particular (preferred) direction, and are inhibited in response to motion in the opposite (anti-preferred) direction. We investigated the responses of LM neurons to sine wave gratings of varying spatial and temporal frequency drifting in the preferred and anti-preferred directions. The LM neurons fell into two categories. "Fast" neurons were maximally excited by gratings of low spatial [0.03-0.25 cycles/ degrees (cpd)] and mid-high temporal frequencies (0.5-16 Hz). "Slow" neurons were maximally excited by gratings of high spatial (0.35-2 cpd) and low-mid temporal frequencies (0.125-2 Hz). Of the slow neurons, all but one preferred forward (temporal to nasal) motion. The fast group included neurons that preferred forward, backward, upward, and downward motion. For most cells (81%), the spatial and temporal frequency that elicited maximal excitation to motion in the preferred direction did not coincide with the spatial and temporal frequency that elicited maximal inhibition to gratings moving in the anti-preferred direction. With respect to motion in the anti-preferred direction, a substantial proportion of the LM neurons (32%) showed bi-directional responses. That is, the spatiotemporal plots contained domains of excitation in addition to the region of inhibition. Neurons tuned to stimulus velocity across different spatial frequency were rare (5%), but some neurons (39%) were tuned to temporal frequency. These results are discussed in relation to previous studies of the responses of neurons in the accessory optic system and pretectum to drifting gratings and other largefield stimuli.

Animals↗
PubMed2006

DNA damage binding protein component DDB1 participates in nucleotide excision repair through DDB2 DNA-binding and cullin 4A ubiquitin ligase activity.

Functional defect in DNA damage binding (DDB) activity has a direct relationship to decreased nucleotide excision repair (NER) and increased susceptibility to cancer. DDB forms a complex with cullin 4A (Cul4A), which is now known to ubiquitylate DDB2, XPC, and histone H2A. However, the exact role of DDB1 in NER is unclear. In this study, we show that DDB1 knockdown in human cells impaired their ability to efficiently repair UV-induced cyclobutane pyrimidine dimers (CPD) but not 6-4 photoproducts (6-4PP). Extensive nuclear protein fractionation and chromatin association analysis revealed that upon irradiation, DDB1 protein is translocated from a loosely bound to a tightly bound in vivo chromatin fraction and the DDB1 translocation required the participation of functional DDB2 protein. DDB1 knockdown also affected the translocation of Cul4A component to the tightly bound form in UV-damaged chromatin in vivo as well as its recruitment to the locally damaged nuclear foci in situ. However, DDB1 knockdown had no effect on DNA damage binding capacity of DDB2. The data indicated that DDB2 can bind to damaged DNA in vivo as a monomer, whereas Cul4A recruitment to damage sites depends on the fully assembled complex. Our data also showed that DDB1 is required for the UV-induced DDB2 ubiquitylation and degradation. In summary, the results suggest that (a) DDB1 is critical for efficient NER of CPD; (b) DDB1 acts in bridging DDB2 and ubiquitin ligase Cul4A; and (c) DDB1 aids in recruiting the ubiquitin ligase activity to the damaged sites for successful commencement of lesion processing by NER.

Cullin Proteins↗
PubMed2006

Prevention of ultraviolet radiation-induced immunosuppression by (-)-epigallocatechin-3-gallate in mice is mediated through interleukin 12-dependent DNA repair.

PURPOSE: Solar UV radiation-induced immunosuppression is considered to be a risk factor for melanoma and nonmelanoma skin cancers. We previously have shown that topical application of (-)-epigallocatechin-3-gallate (EGCG) prevents UV-induced immunosuppression in mice. We studied whether prevention of UV-induced immunosuppression by EGCG is mediated through interleukin 12 (IL-12)-dependent DNA repair. EXPERIMENTAL DESIGN: IL-12 knockout (KO) mice on C3H/HeN background and DNA repair-deficient cells from xeroderma pigmentosum complementation group A (XPA) patients were used in this study. The effect of EGCG was determined on UV-induced suppression of contact hypersensitivity and UV-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPD) in mice and XPA-deficient cells using immunohistochemistry and dot-blot analysis. RESULTS: Topical treatment with EGCG prevented UV-induced suppression of the contact hypersensitivity in wild-type (WT) mice but did not prevent it in IL-12 KO mice. Injection of anti-IL-12 monoclonal antibody to WT mice blocked the preventive effect of EGCG on UV-induced immunosuppression. EGCG reduced or repaired UV-induced DNA damage in skin faster in WT mice as shown by reduced number of CPDs(+) cells and reduced the migration of CPD(+) antigen-presenting cells from the skin to draining lymph nodes. In contrast, this effect of EGCG was not seen in IL-12 KO mice. Further, EGCG was able to repair UV-induced CPDs in XPA-proficient cells obtained from healthy person but did not repair in XPA-deficient cells, indicating that nucleotide excision repair mechanism is involved in DNA repair. CONCLUSIONS: These data identify a new mechanism by which EGCG prevents UV-induced immunosuppression, and this may contribute to the chemopreventive activity of EGCG in prevention of photocarcinogenesis.

Administration, Topical↗
PubMed1978

Effects of age of blinding on rhythmic pituitary-adrenal function in female rats.

These experiments were designed to study the effects of age of blinding on the circadian rhythm in pituitary-adrenal function in female rats. In the 1st experiment, the eyes were removed at 1 day of age and serial blood samples were obtained at 6-h intervals for 24 h at 45 days. In the 2nd experiment, rats were blinded at 1,26 or 60 days of age, and serial blood samples were collected at 4-h intervals for 44 h when the rats were 84, 112 and 142 days of age. Intact and sham-operated rats served as controls. Plasma corticosterone (cpd B) concentrations, measured fluorometrically, were used to assess pituitary-adrenal function. Blinding disrupted cpd B patterns in all groups on all occasions. However, steroid patterns of individual rats suggested the presence of free-running 24-h rhythms. This suggestion was supported by the results of aligning the steroid peaks of individual blinded rats. This procedure yielded group patterns of steroid levels which were comparable to those of controls. The periodic stimuli available to the blinded rats from intact rats in the same and adjacent cages did not synchronize this rhythm. These results suggest that the eyes and their central projections are not essential after birth for the development and maintenance of rhythmic pituitary-adrenal function; these structures appear necessary, however, for synchronization with light-dark cycles.

Age Factors↗
PubMed1990

Decrease in hepatic mitochondrial redox state by massive infusion of citrate-phosphate-dextrose solution in jaundiced rabbits.

To clarify the mechanism of metabolic derangement by massive blood transfusion to the damaged liver, the changes in the hepatic mitochondrial redox state, as reflected in arterial ketone body ratio (acetoacetate/3-hydroxybutyrate), were studied in jaundiced rabbits by infusion of massive citrate-phosphate-dextrose (CPD) solution. The jaundiced rabbits received common bile duct ligation (BDL group), and the sham group had a simple exploration of the bile duct. CPD solution was infused for 3 h at a rate of 9 ml/kg/h in each group. As metabolic parameters, blood gas, pyruvate, lactate, citrate and ketone body ratio were analyzed in the arterial blood. During the course, arterial ketone body ratio decreased significantly (p less than 0.01) in the BDL group with severe metabolic acidosis, while it was maintained at high value in the sham group with metabolic alkalosis. Organic acids were more highly accumulated in the BDL group than in the sham group. These results suggested a hepatodepressant effect of massive blood transfusion, especially in the damaged liver.

Acidosis↗
PubMed1986

Hypoxemia during hemodialysis in patients with impairment in pulmonary function.

In order to examine the effect of different dialysates on hemodialysis-induced hypoxemia, 6 stable patients with chronic pulmonary disease (CPD) were compared with 8 control subjects using, alternately, acetate and bicarbonate in the dialysate. These patients were also studied during acetate dialysis and 2 liters/min of nasally administered oxygen. In the control group the presence of hypoxemia with acetate and its absence with bicarbonate suggests that the major mechanism responsible for hypoxemia is hypoventilation. In CPD patients the higher hypoxemia with acetate which bicarbonate analysis did not prevent suggests that a superimposed mechanism may be an important factor in hypoxia aggravation. In these patients hypoxemia can be prevented easily by increasing the inspired oxygen concentration.

Acetates↗
PubMed1994

The pulmonary vascular response to acute hypoxia in chronic pulmonary disease: morphological assessment with magnified pulmonary wedge angiography.

To detect hypoxic pulmonary vasoconstriction (HPV) morphologically, we investigated the pulmonary vascular response to acute hypoxia in 27 patients with chronic pulmonary disease (CPD) and 8 healthy subjects. Pulmonary hemodynamic measurements and magnified pulmonary wedge angiography (MPWA) were carried out before and after inhalation of 13% oxygen in nitrogen for 15 min. The diameters of central arteries (A) and muscular arteries (B) were measured using a densitometric method. Vasoconstriction was detected in the muscular arteries than in the central arteries by MPWA. There was a significant correlation between delta P (changes of mean PA pressure) and delta B/A (changes in diameters of B/A) in the CPD group. A significant correlation was found between delta SvO2 and delta B/A in the control group. We conclude that MPWA was a very useful method for the simple detection of HPV in patients with CPDs and we detected one site of HPV on the ninth generation of the pulmonary arterial tree by MPWA.

Adult↗
PubMed1995

Monitoring of nocturnal oxygen desaturation using pulse oximeter and apnomonitor in patients with chronic pulmonary disease.

The relationship between the degree of nocturnal oxygen desaturation (NOD) and pulmonary hemodynamics, pulmonary function tests, and resting awake blood gases was evaluated in patients with chronic pulmonary diseases (CPD). The severity of NOD correlated with the degree of impairment of pulmonary hemodynamics, but not with pulmonary function tests or resting awake blood gases. NOD was markedly alleviated by oxygen inhalation in CPD patients who did not develop sleep apnea.

Aged↗
PubMed1980

Susceptibility of anaerobic bacteria in vitro to 23 antimicrobial agents.

589 isolates of anaerobic bacteria, including 127 isolates of Bacterioides fracilis, were tested against 23 antimicrobial agents. At their usually achievable serum levels, carbenicillin, ticarcillin, mezlocillin and piperacillin; cefoxitin, minocycline, doxycycline, clindamycin, chloramphenicol and rifampin were effective against more than 80% of B. fragilis isolates. At usual therapeutic doses, penicillin (PEN), ampicillin (AMP), cyclacillin (CYC), cephalothin (CT), cefazolin (CZ), cephradine (CPD), cefamandole (CMD), cefaclor (CCL), cefuroxime (CRX), spectinomycin (SPT), tetracycline (TET), ethambutol (EMB) and isoniazid (INH) were ineffective against B. Fragilis. However, high and clinically tolerated doses of PEN, CMD and SPT inhibited more than 80% of B. fragilis isolates, but AMP, CYC, CT, CZ, CPD, CCL and CRX, TET, EMB and INH remained totally ineffective against B. fragilis. The therapeutic merits of these antibiotics are discussed.

Anaerobiosis↗
PubMed1991

Effect of blood transfusion on acid base, glucose and electrolyte status in very low birth weight infants.

The effect of citrate phosphate dextrose (CPD) blood transfusion on the acid base, glucose and electrolyte status of VLBW infants was studied in infants aged 1-7, 8-20 and greater than 20 days; a 4th group composed of infants greater than 20 days subjected to a second transfusion was also studied. All the infants remained clinically well during and after the transfusion. Only the infants in the group 1-7 days experienced a significant fall in ionic Ca and PO2. No significant change in all the other parameters studied was observed. In the other groups of infants studied, the changes observed were not significant, and became less with increasing age and repeat transfusion. VLBW infants apparently tolerate CPD blood transfusion well.

Acid-Base Equilibrium↗
PubMed1982

The constituents of fresh frozen plasma stored with citrate phosphate dextrose and their clinical implications.

The authors have investigated the constituents of fresh frozen plasma stored in citrate phosphate dextrose (CPD) at -20 degrees C. The results indicate abnormal characteristics of several of the constituents, whereas some others remain within normal values. This is attributed to preparation procedures with the addition of a CPD solution. Fresh frozen plasma being hyperosmolal, hypernatremic, hyperglycemic, hyperphosphatemic, normokalemic and containing normal values of protein, calcium, magnesium, and water carries a clinical implication for the physician as a guide for the treatment of the critically ill patient when large amounts of plasma are needed.

Blood Glucose↗
PubMed2000

Cortical potential distributions and information processing.

The use of sets of spatiotemporal cortical potential distributions (CPDs) as the basis for cognitive information processing results in a very large space of cognitive elements with natural metrics. Results obtained from current source density (CSD) analysis suggest that in the CPD picture, action potentials may make only a relatively minor contribution to the brain's code. In order to establish if two CPDs are close, we consider standard metrics in spaces of continuous functions, and these may be employed to ascertain if two stimuli will be identified as the same. The correspondence between the electrical activity within brain regions, including not only action potentials but all postsynaptic potentials (PSPs), and CPDs is considered. We examine the possibility of using the CSD approach to find potential distributions using the descriptive approach in which precise sets of times are ascribed to the occurrence of action potentials and PSPs. Using metrics in the multidimensional space of paths of collections of point processes, we show that closeness of CPDs is implied by closeness of sets of spike times and PSP times if a certain metric is used but not others. We also set forth a dynamical model consisting of a system of reaction-dif fusion equations for ionic concentrations coupled with nerve membrane potential equations and active transport systems. Making the approximation of a descriptive approach, the correspondence between sets of spike times and PSP times and CPDs is obtained as with the CSD method. However, since it is not possible to ascribe precise times to the occurrence of PSPs and action potentials, the descriptive approach cannot be used to describe the configuration of electrical activity in cortical regions accurately. We also discuss how the CPD framework relates to the binding problem and submillisecond timing.

Algorithms↗
PubMed2005

Chromatic and luminance contrast sensitivities in asymptomatic carriers from a large Brazilian pedigree of 11778 Leber hereditary optic neuropathy.

PURPOSE: To determine whether asymptomatic 11778 LHON carriers demonstrated impairments in (1) chromatic red/green (R/G) and blue/yellow (B/Y) contrast sensitivity functions (CSF) and in (2) luminance contrast sensitivity functions in the spatial CSF (SCSF) and temporal CSF (TCSF) domains. METHODS: Twenty-five carriers (8 male, 17 female; 34.1 +/- 15.1 years of age) of homoplasmic 11778 LHON from the same well-described family and 30 age-matched controls (17 male, 13 female; 29.2 +/- 7.1 years of age) were tested in one eye, randomly selected. Of the 25 eyes tested, 18 had normal fundus, 5 had swelling and microangiopathy, and 2 had temporal pallor. The R/G and B/Y CSFs were obtained after equiluminance correction with bichromatic horizontal sinusoidal gratings at 0.3, 0.7, and 2 cycles per degree (cpd); the SCSFs were obtained with achromatic gratings at 0.3, 2, 6, and 12 cpd; and the TCSFs were obtained at 2, 10, 20, and 33 Hz with sinusoidal modulation of a 2.7 degrees field with a superimposed spatial Gabor function. RESULTS: Differences between carriers and controls were statistically significant for all spatial frequencies of chromatic and luminance SCSFs, but not for the TCSFs. R/G equiluminance settings of carriers differed from those of controls (P < 0.001), requiring higher luminance in the green; B/Y equiluminance settings were not statistically different in carriers and controls. Fundus findings did not correlate with CS results. CONCLUSIONS: Luminance and chromatic spatial CS losses that affected all tested spatial frequencies, are reported in LHON asymptomatic carriers with the mtDNA 11778 mutation. No losses were found in the temporal CSF. An intriguing finding is that the blue system is substantially spared in this LHON family. These represent subclinical visual impairments in otherwise asymptomatic LHON carriers.

Adolescent↗
PubMed1998

Mouse-specific carcinogens: an assessment of hazard and significance for validation of short-term carcinogenicity bioassays in transgenic mice.

1. The International Conference on the Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for human use (ICH) has agreed that bioassay data from only one species, the rat, supported by appropriate mutagenicity and pharmacokinetic data and also information from new (unvalidated) short term in vivo screening tests for potential carcinogenicity, could be used for the licensing of human medicines. This proposal has been supported by reviews of the utility of testing pharmaceuticals in the mouse which have concluded that the mouse bioassay contributes little to regulatory decisions. The current review was undertaken to identify 'genuine' mouse-specific carcinogens using the Gold Carcinogenicity Potency Database (CPD) for the initial identification of potential mouse-specific carcinogens from published literature. Hazard assessments were completed for these chemicals with particular attention focused on the 'genuine' mouse-specific carcinogens. The significance of such chemicals has been discussed together with consideration of on-going work on the validation of short-term carcinogenicity bioassays using transgenic mice. 2. Seventy-six potential mouse specific carcinogens were identified through the Gold Carcinogenicity Potency Database. Following more detailed consideration a total of ten chemicals were excluded from further consideration (three were multispecies carcinogens, five were considered to be non-carcinogenic in the mouse, and the data for two were uninterpretable). The review focused on the remaining 66 chemicals. There was equivocal evidence of carcinogenicity to the rat for 28 chemicals and inadequate data for a further 23 chemicals. Fifteen 'genuine' mouse-specific carcinogens were identified. These 15 chemicals comprise two genotoxic mouse-specific carcinogens (N-methylolacrylamide (924-42-5), 2,6-Dichloro-p-phenylenediamine (609-20-1); five non-genotoxic mouse-specific carcinogens 2-Aminobiphenyl.HCl (2185-92-4), Captan (133-06-2), Dieldrin (60-57-7), Diethylhexyladipate (103-23-1), and Probenicid (57-66-9); five mouse-specific carcinogens with equivocal evidence of mutagenicity were identified; (2,4-diaminophenol.2HCl (137-09-7), Dipyrone (68-89-3), Ozone (10028-15-6), Vinylidene chloride (75-35-4), and Zearalenone (17924-92-4)), and three mouse-specific carcinogens with inadequate mutagenicity data (Benzaldehyde (100-52-7), Piperonyl sulphoxide (120-62-7), Ripazepam (26308-28-1)). 3. It is suggested that the two genotoxic mouse carcinogens would have been considered as potential carcinogens in the absence of a mouse bioassay. Of the five non-genotoxic mouse-specific carcinogens; three induced tumours in mouse liver only and are considered as being of low potential hazard to human health. The remaining two chemicals would have been missed in the absence of a mouse bioassay (2-aminobiphenyl (2185-92-4) and captan (133-06-2)) and thus are good candidates for evaluation in the short term bioassays in transgenic mice currently being validated. 4. The hardest group of mouse-specific carcinogens to evaluate are those for which there is equivocal or inadequate mutagenicity data. The difficulty in evaluating these particular chemicals emphasises the need for adequate mutagenicity data in addition to adequate carcinogenicity data in order to assess potential hazards to human health. Hazard assessments and a consideration of the potential role for short-term bioassays in transgenic mice for the eight chemicals in this subgroup are presented. 5. A number of general conclusions have been derived from this review. Firstly, there are insufficient published genotoxicity data to allow a full assessment fo mutagenic potential for 57/76 of the potential mouse-specific carcinogens identified from the CPD. This is surprising given the clear value of such data in interpreting bioassay results and the much greater resources required for carcinogenicity bioassays. (ABSTRACT TRUNCATED)

Animals↗