Can we predict the neutral breast position using the gravity-loaded breast position, age, anthropometrics and breast composition data?

BACKGROUND: This study aimed to identify the predictor variables which account for neutral breast position variance using a full independent variable dataset (the gravity-loaded breast position, age and anthropometrics, and magnetic resonance imaging breast composition data), and a simplified independent variable dataset (magnetic resonance imaging breast composition data excluded). METHODS: Breast position (three-dimensional neutral and static gravity-loaded), age, anthropometrics and magnetic resonance imaging breast composition data were collected for 80 females (bra size 32A to 38D). Correlations between the neutral breast position and the gravity-loaded breast position, age, anthropometrics, and magnetic resonance imaging breast composition data were assessed. Multiple linear and multivariate multiple regression models were utilised to predict neutral breast positions, with mean absolute differences and root mean square error comparing observed and predicted neutral breast positions. FINDINGS: Breast volume was the only breast composition variable to contribute as a predictor of the neutral breast position. While ≥69% of the variance in the anteroposterior and mediolateral neutral breast positions were accounted for utilising the gravity-loaded breast position, multivariate multiple regression modelling resulted in mean absolute differences >5 mm. INTERPRETATION: Due to the marginal contribution of breast composition data, a full independent variable dataset may be unnecessary for this application. Additionally, the gravity-loaded breast position, age, anthropometrics, and breast composition data do not successfully predict the neutral breast position. Incorporation of the neutral breast position into breast support garments may enhance bra development. However, further identification of variables which predict the neutral breast position is required.

Controlled Release Dinoprostone Insert and Foley Compared to Foley Alone: A Randomized Pilot Trial.

OBJECTIVE: The aim of study is to compare, in a pilot study, combined dinoprostone vaginal insert and Foley catheter (DVI + Foley) with Foley alone (Foley) for cervical ripening and labor induction at term. STUDY DESIGN: In this open-label pilot randomized controlled trial, women not in labor, with intact membranes, no prior uterine incision, an unfavorable cervix, gestational age ≥37 weeks, and a live, nonanomalous singleton fetus in cephalic presentation were randomly assigned, stratified by parity, to DVI + Foley or Foley. Oxytocin was used in both groups after cervical ripening. Primary outcome was time to vaginal delivery. RESULTS: From April 2017 to January 2018, 100 women were randomized. Median (25-75th percentile) time to vaginal delivery for nulliparous women was 21.2 (16.6-38.0) hours with DVI + Foley (n = 26) compared with 31.3 (23.3-46.9) hours with Foley (n = 24) (Wilcoxon p = 0.05). Median time to vaginal delivery for parous women was 17.1 (13.6-21.9) hours with DVI + Foley (n = 25) compared with 14.8 (12.7-19.5) hours with Foley (n = 25) (Wilcoxon p = 0.21). Results were also analyzed to consider the competing risk of cesarean using cumulative incidence functions. CONCLUSION: Compared with Foley alone, combined use of the dinoprostone vaginal insert and Foley for cervical ripening may shorten time to vaginal delivery for nulliparous but not parous women.

How the characteristics of sports bras affect their performance.

Breast movement reduction (%) measures breast support and sports bra performance, however limited evidence exists on the sports bra characteristics which affect it. This study investigated breast movement reduction achieved by 98 sports bras, the categorisation of support levels, and the characteristics that contribute. Each bra was tested on ∼12 females (total n = 77). Relative breast position was recorded during sports bra and bare-breasted running, and breast movement reduction calculated; low, medium, high breast support tertiles were identified and compared to brand-classified support levels. Ten bra characteristics were identified, and regressions determined which characteristics contributed to performance. Breast movement reduction ranged from 36% to 74%; 69% of bras marketed as high support were in the high support tertile (>63%). Encapsulation style, padded cups, nylon, adjustable underband and high neck drop accounted for 37.1% of breast movement reduction variance. Findings facilitate high performance sports bra development and inform consumer choice. Practitioner summary: Little is known about the biomechanical breast support which sports bras actually provide. This original research facilitates high performance sports bra development, and helps inform consumer choice, by identifying the breast movement reduction of a large sample of sports bras, and the characteristics which impact sports bra performance. Abbreviations: A-P: anterior-posterior; BMI: body mass index; C7: 7th cervical vertebrae; LNIP: left nipple; M-L: medial-lateral; PX: xiphoid process; ROM: range of motion; S-I: superior-inferior; SD: standard deviation; STN: suprasternal notch; T8: 8th thoracic vertebrae.

Do static and dynamic activities induce potentially damaging breast skin strain?

BACKGROUND/AIM: This study aimed to quantify breast skin strain and strain rate and the effect of support garments at reducing strain and to determine characteristics that correlate with strain during static and dynamic activity. METHODS: 39 women (UK size 32C to 36G) had electromagnetic sensors applied to their breast skin. Sensor coordinates were recorded while standing, walking, running, in no, low and high breast support conditions, plus bare-breasted in the estimated neutral position to calculate strain. Relative breast coordinates and 35 inter-sensor distances identified peak breast skin strain (%) and strain rate (%·s-1), which were then correlated with nipple kinematics, breast pain and participant characteristics. RESULTS: Mean peak breast skin strain was generally <60% during standing, walking and running; however, some individuals exhibited 93% strain in bare-breasted running. Compared with low support, high support did not further reduce strain during standing and walking. Peak breast skin strain/strain rate location was longitudinal, in lateral and medial breast regions and displayed strong correlations with breast volume, body mass index and bust circumference. CONCLUSION: Static and dynamic activity did not result in excessive breast skin strain, suggesting low risk of skin damage. However, during running, some individuals experienced excessive skin strains (up to 93%) and strain rates (up to 1258%·s-1). Breast skin strain/strain rate location suggests lift is required in the lateral and medial bra cup to reduce strain, particularly in larger breast volumes due to increased skin strain risk.

The Kinematics of Breasts Implanted With a Reduced Mass Implant: A Pilot Study.

BACKGROUND: Breast implants may increase breast skin tension and interact with surrounding tissues to alter breast position and motion during dynamic activity. Reducing implant mass and changing implant location (submuscular/subglandular) may also affect breast kinematics and the subsequent loads on breast structures. OBJECTIVES: The aim of this pilot study was to describe the kinematics of breasts augmented with reduced-mass implants during standing, walking, and running, compared with natural breasts, and to provide insight into how implant location (submuscular/subglandular) alters breast kinematics. METHODS: Two breast augmentation participants (12-15 months postsurgery: 32AA presurgery, anatomical submuscular 255 cc B-Lite reduced-mass implant; 32A presurgery, anatomical subglandular 285 cc B-Lite reduced-mass implant) and 2 natural-breasted participants of similar breast size and anthropometrics were recruited. Nipple and torso positional data were recorded with electromagnetic sensors during standing, walking, and running. Nipple kinematics relative to the torso were calculated. RESULTS: The B-Lite participants both displayed greater nipple projection and elevation during standing and a 50% reduction in nipple acceleration during walking, when compared with their natural counterparts. During running, the B-Lite subglandular participant displayed decreased nipple kinematics compared with her natural counterpart and lower nipple kinematics compared with the B-Lite submuscular participant during walking and running. CONCLUSIONS: A combination of implant location (subglandular) and reduced mass minimized nipple kinematics during running. Reducing nipple kinematics during dynamic activity may decrease the loading on breast structures, helping to decrease ptosis and increase the longevity of procedure outcomes.

Marathon Pace Control in Masters Athletes.

PURPOSE: Pacing strategies are key to overall performance outcome in distance-running events. Presently, no literature has examined pacing strategies used by masters athletes of all running levels during a competitive marathon. Therefore, this study aimed to examine masters athletes' pacing strategies, categorized by gender, age, and performance level. METHODS: Data were retrieved from the 2015 TSC New York City Marathon for 31,762 masters athletes (20,019 men and 11,743 women). Seven performance-classification (PC) groupings were identified via comparison of overall completion time compared with current world records, appropriate to age and gender. Data were categorized via, age, gender, and performance level. Mean 5-km speed for the initial 40 km was calculated, and the fastest and slowest 5-km-split speeds were identified and expressed as a percentage faster or slower than mean speed. Pace range, calculated as the absolute sum of the fastest and slowest split percentages, was then analyzed. RESULTS: Significant main effects were identified for age, gender, and performance level (P < .001), with performance level the most determining factor. Athletes in PC1 displayed the lowest pace range (14.19% ± 6.66%), and as the performance levels of athletes decreased, pace range increased linearly (PC2-PC7, 17.52% ± 9.14% to 36.42% ± 18.32%). A significant interaction effect was found for gender × performance (P < .001), with women showing a smaller pace range (-3.81%). CONCLUSIONS: High-performing masters athletes use more-controlled pacing strategies than their lower-ranked counterparts during a competitive marathon, independent of age and gender.

Quantification of gravity-induced skin strain across the breast surface.

BACKGROUND: Quantification of the magnitude of skin strain in different regions of the breast may help to estimate possible gravity-induced damage whilst also being able to inform the selection of incision locations during breast surgery. The aim of this study was to quantify static skin strain over the breast surface and to estimate the risk of skin damage caused by gravitational loading. METHODS: Fourteen participants had 21 markers applied to their torso and left breast. The non-gravity breast position was estimated as the mid-point of the breast positions in water and soybean oil (higher and lower density than breast respectively). The static gravity-loaded breast position was also measured. Skin strain was calculated as the percentage extension between adjacent breast markers in the gravity and non-gravity loaded conditions. FINDINGS: Gravity induced breast deformation caused peak strains ranging from 14 to 75% across participants, with potentially damaging skin strain (>60%) in one participant and skin strains above 30% (skin resistance zone) in a further four participants. These peak strain values all occurred in the longitudinal direction in the upper region of the breast skin. In the latitudinal direction, smaller-breasted participants experienced greater strain on the outer (lateral) breast regions and less strain on the inner (medial) breast regions, a trend which was reversed in the larger breasted participants (above size 34D). INTERPRETATION: To reduce tension on surgical incisions it is suggested that preference should be given to medial latitudinal locations for smaller breasted women and lateral latitudinal locations for larger breasted women.

Minimum number of days required for a reliable estimate of daily step count and energy expenditure, in people with MS who walk unaided.

BACKGROUND AND PURPOSE: The purpose of this study was to examine the minimum number of days needed to reliably estimate daily step count and energy expenditure (EE), in people with multiple sclerosis (MS) who walked unaided. METHODS: Seven days of activity monitor data were collected for 26 participants with MS (age=44.5±11.9years; time since diagnosis=6.5±6.2years; Patient Determined Disease Steps=≤3). Mean daily step count and mean daily EE (kcal) were calculated for all combinations of days (127 combinations), and compared to the respective 7-day mean daily step count or mean daily EE using intra-class correlations (ICC), the Generalizability Theory and Bland-Altman. RESULTS: For step count, ICC values of 0.94-0.98 and a G-coefficient of 0.81 indicate a minimum of any random 2-day combination is required to reliably calculate mean daily step count. For EE, ICC values of 0.96-0.99 and a G-coefficient of 0.83 indicate a minimum of any random 4-day combination is required to reliably calculate mean daily EE. For Bland-Altman analyses all combinations of days, bar single day combinations, resulted in a mean bias within ±10%, when expressed as a percentage of the 7-day mean daily step count or mean daily EE. CONCLUSIONS: A minimum of 2days for step count and 4days for EE, regardless of day type, is needed to reliably estimate daily step count and daily EE, in people with MS who walk unaided.

Subchronic perfluorooctanesulfonate (PFOS) exposure induces elevated mutant frequency in an in vivo λ transgenic medaka mutation assay.

Perfluorooctanesulfonate (PFOS) has been widely detected in the environment, wildlife and humans, but few studies have ever examined its mutagenic effect in vivo. In the present study, we use a transgenic fish model, the λ transgenic medaka, to evaluate the potential mutagenicity of PFOS in vivo following a subchronic exposure of 30 days. The mutant frequency of cII target gene was 3.46 × 10-5 in liver tissue from control fish, which increased by 1.4-fold to 4.86 × 10-5 in fish exposed to 6.7 µg/L PFOS, 1.55-fold to 5.36 × 10-5 in fish exposed to 27.6 µg/L PFOS, and 2.02-fold to 6.99 × 10-5 in fish exposed to 87.6 µg/L PFOS. This dose-dependent increase of mutant frequency was also accompanied with mutational spectrum changes associated with PFOS exposure. In particular, PFOS-induced mutation was characterized by +1 frameshift mutations, which increased from 0% in control fish to 13.2% in fish exposed to 27.6 µg/L PFOS and 14.6% in fish exposed to 87.6 µg/L PFOS. Our findings provide the first evidence of PFOS's mutagenicity in an aquatic model system. Given the fact that most conventional mutagenic assays were negative for PFOS, we propose that PFOS-induced mutation in liver tissue of λ transgenic medaka may be mediated through compromised liver function.

Comparison of accelerometry stride time calculation methods.

Inertial sensors such as accelerometers and gyroscopes can provide a multitude of information on running gait. Running parameters such as stride time and ground contact time can all be identified within tibial accelerometry data. Within this, stride time is a popular parameter of interest, possibly due to its role in running economy. However, there are multiple methods utilised to derive stride time from tibial accelerometry data, some of which may offer complications when implemented on larger data files. Therefore, the purpose of this study was to compare previously utilised methods of stride time derivation to an original proposed method, utilising medio-lateral tibial acceleration data filtered at 2Hz, allowing for greater efficiency in stride time output. Tibial accelerometry data from six participants training for a half marathon were utilised. One right leg run was randomly selected for each participant, in which five consecutive running stride times were calculated. Four calculation methods were employed to derive stride time. A repeated measures analysis of variance (ANOVA) identified no significant difference in stride time between stride time calculation methods (p=1.00), whilst intra-class coefficient values (all >0.95) and coefficient of variance values (all <1.5%) indicate good reliability. Results indicate that the proposed method possibly offers a simplified technique for stride time output during running gait analysis. This method may be less influenced by "double peak" error and minor fluctuations within the data, allowing for accurate and efficient automated data output in both real time and post processing.

Spatial distribution of lead in Sacramento, California, USA.

Chronic exposure to lead remains a health concern in many urban areas; Sacramento, California is one example, with state surveillance data showing nearly 3% of screened children reported with blood lead levels over 4.5 µg/dL in 2009. To investigate the environmental exposure, 91 soil samples were collected and analyzed by ICP-AES and ICP-MS for 14 elements. An additional 28 samples were collected from areas of focus and analyzed by hand-held X-ray fluorescence spectrometry for Pb and Zn. Analysis of the metals data revealed non-normal distributions and positive skewness, consistent with anthropogenic input. In addition, high correlation coefficients (≥0.75) of metal concentrations in Cd-Pb, Cd-Zn, Pb-Zn, and Sb-Sn pairs suggest similarities in the input mechanisms. Semivariograms generated from Pb and associated metals reveal these metals to exhibit spatial correlation. A prediction map of lead concentrations in soil was generated by ordinary kriging, showing elevated concentrations in soil located in the central, older area of Sacramento where historic traffic density and industrial activity have been historically concentrated. XRF analysis of Pb and Zn from additional samples verifies elevated concentrations in the central areas of Sacramento as predicted.

Prediction of province-level outbreaks of foot-and-mouth disease in Iran using a zero-inflated negative binomial model.

To identify events that could predict province-level frequency of foot-and-mouth disease (FMD) outbreaks in Iran, 5707 outbreaks reported from April 1995 to March 2002 were studied. A zero-inflated negative binomial model was used to estimate the probability of a 'no-outbreak' status and the number of outbreaks in a province, using the number of previous occurrences of FMD for the same or adjacent provinces and season as covariates. For each province, the probability of observing no outbreak was negatively associated with the number of outbreaks in the same province in the previous month (odds ratio [OR]=0.06, 95% confidence interval [CI]: 0.01, 0.30) and in 'the second previous month' (OR=0.10, 95% CI: 0.02, 0.51), the total number of outbreaks in the second previous month in adjacent provinces (OR=0.57, 95% CI: 0.36, 0.91) and the season (winter [OR=0.18, 95% CI: 0.06, 0.55] and spring [OR=0.27, 95% CI: 0.09, 0.81], compared with summer). The expected number of outbreaks in a province was positively associated with number of outbreaks in the same province in previous month (coefficient [coef]=0.74, 95% CI: 0.66, 0.82) and in the second previous month (coef=0.23, 95% CI: 0.16, 0.31), total number of outbreaks in adjacent provinces in the previous month (coef=0.32, 95% CI: 0.22, 0.41) and season (fall [coef=0.20, 95% CI: 0.07, 0.33] and spring [coef=0.18, 95% CI: 0.05, 0.31], compared to summer); however, number of outbreaks was negatively associated with the total number of outbreaks in adjacent provinces in the second previous month (coef=-0.19, 95% CI: -0.28, -0.09). The findings indicate that the probability of an outbreak (and the expected number of outbreaks if any) may be predicted based on previous province information, which could help decision-makers allocate resources more efficiently for province-level disease control measures. Further, the study illustrates use of zero inflated negative binomial model to study diseases occurrence where disease is infrequently observed.

Evaluation of cryoprotectant and cooling rate for sperm cryopreservation in the euryhaline fish medaka Oryzias latipes.

Medaka Oryzias latipes is a well-recognized biomedical fish model because of advantageous features such as small body size, transparency of embryos, and established techniques for gene knockout and modification. The goal of this study was to evaluate two critical factors, cryoprotectant and cooling rate, for sperm cryopreservation in 0.25-ml French straws. The objectives were to: (1) evaluate the acute toxicity of methanol, 2-methoxyethanol (ME), dimethyl sulfoxide (Me(2)SO), N,N-dimethylacetamide (DMA), N,N-dimethyl formamide (DMF), and glycerol with concentrations of 5%, 10%, and 15% for 60min of incubation at 4°C; (2) evaluate cooling rates from 5 to 25°C/min for freezing and their interaction with cryoprotectants, and (3) test fertility of thawed sperm cryopreserved with selected cryoprotectants and associated cooling rates. Evaluation of cryoprotectant toxicity showed that methanol and ME (5% and 10%) did not change the sperm motility after 30min; Me(2)SO, DMA, and DMF (10% and 15%) and glycerol (5%, 10% and 15%) significantly decreased the motility of sperm within 1min after mixing. Based on these results, methanol and ME were selected as cryoprotectants (10%) to evaluate with different cooling rates (from 5 to 25°C/min) and were compared to Me(2)SO and DMF (10%) (based on their use as cryoprotectants in previous publications). Post-thaw motility was affected by cryoprotectant, cooling rate, and their interaction (P⩽0.000). The highest post-thaw motility (50±10%) was observed at a cooling rate of 10°C/min with methanol as cryoprotectant. Comparable post-thaw motility (37±12%) was obtained at a cooling rate of 15°C/min with ME as cryoprotectant. With DMF, post-thaw motility at all cooling rates was ⩽10% which was significantly lower than that of methanol and ME. With Me(2)SO, post-thaw motilities were less than 1% at all cooling rates, and significantly lower compared to the other three cryoprotectants (P⩽0.000). When sperm from individual males were cryopreserved with 10% methanol at a cooling rate of 10°C/min and 10% ME with a rate of 15°C/min, no difference was found in post-thaw motility. Fertility testing of thawed sperm cryopreserved with 10% methanol at a rate of 10°C/min showed average hatching of 70±30% which was comparable to that of fresh sperm (86±15%). Overall, this study established a baseline for high-throughput sperm cryopreservation of medaka provides an outline for protocol standardization and use of automated processing equipment in the future.

Isolated spermatozoa as indicators of mutations transmitted to progeny.

Spermatozoa comprise a large and homogeneous population of cells that may serve as an alternative to resource-intensive assays of transmissible mutations based on progeny. To evaluate mutagenic responses in spermatozoa derived from germ cells exposed to a mutagen at different stages of spermatogenesis, we compared cII mutant frequencies (MFs) in spermatozoa collected from male lambda transgenic medaka exposed to ethylnitrosourea (ENU) as either post-meiotic or pre-meiotic germ cells. cII MFs in spermatozoa exposed to ENU as spermatogonial stem cells were induced significantly, 9-fold, compared to controls, whereas, cII MFs in spermatozoa exposed as spermatozoa/late spermatids were not elevated. To directly compare responses in spermatozoa with those in progeny, we analyzed cII MFs directly in spermatozoa and in the offspring produced from identical sperm samples of ENU-exposed males. cII MFs in isolated spermatozoa exposed to ENU as post-meiotic germ cells were not significantly elevated, whereas 11-30% of the progeny derived from the identically exposed germ cells exhibited significantly elevated cII MFs, approximately 2-fold to >130-fold, compared to controls. The contradictory responses between spermatozoa and progeny analyses can be attributed to induced pre-mutational lesions that remain intact in spermatozoa but were not detected as mutations. Progeny analyses, by contrast, revealed mutant individuals with elevated cII mutant frequencies because persistent DNA damage in the spermatozoa was fixed as mutations in cells of the early stage embryo. Spermatozoa exposed to a mutagen as spermatogonial stem cells can provide an efficient means to detect the portion of transmissible mutations that were fixed as mutations in spermatozoa. The caveat is that direct analyses of mutations in spermatozoa excludes the contribution of mutations that arise from post-fertilization processes in cells of early stage embryos, and therefore may underestimate the actual frequency of mutant offspring.

Chronic Mycobacterium marinum infection acts as a tumor promoter in Japanese Medaka (Oryzias latipes).

An accumulating body of research indicates there is an increased cancer risk associated with chronic infections. The genus Mycobacterium contains a number of species, including M. tuberculosis, which mount chronic infections and have been implicated in higher cancer risk. Several non-tuberculosis mycobacterial species, including M. marinum, are known to cause chronic infections in fish and like human tuberculosis, often go undetected. The elevated carcinogenic potential for fish colonies infected with Mycobacterium spp. could have far reaching implications because fish models are widely used to study human diseases. Japanese medaka (Oryzias latipes) is an established laboratory fish model for toxicology, mutagenesis, and carcinogenesis; and produces a chronic tuberculosis-like disease when infected by M. marinum. We examined the role that chronic mycobacterial infections play in cancer risk for medaka. Experimental M. marinum infections of medaka alone did not increase the mutational loads or proliferative lesion incidence in all tissues examined. However, we showed that chronic M. marinum infections increased hepatocellular proliferative lesions in fish also exposed to low doses of the mutagen benzo[a]pyrene. These results indicate that chronic mycobacterial infections of medaka are acting as tumor promoters and thereby suggest increased human risks for cancer promotion in human populations burdened with chronic tuberculosis infections.

Upregulation of telomerase function during tissue regeneration.

Telomerase plays a primary role in the maintenance of telomeres in immortal, germ, and tumor cells in humans but is lacking in most somatic cells and tissues. However, many species, including fish and inbred mice, express telomerase in most cells and tissues. Little is known about the expression of telomerase in aquatic species, although the importance of telomerase for longevity has been suggested. We compared telomerase activity and telomere lengths among a broad range of tissues from aquatic species and found telomerase at significant levels in both long- and short-lived aquatic species, suggesting constitutive telomerase expression has an alternative function. Telomere lengths in these aquatic species were comparable to those observed in normal human tissues and cell strains. Given that a host of aquatic species with short life spans have telomerase and a tremendous capacity to regenerate, we tested the hypothesis that telomerase upregulation is important for tissue regeneration. During regeneration, telomerase activity was upregulated and telomere lengths are maintained with the shortest telomeres being elongated, indicating the importance for maintaining telomere length and integrity during tissue regeneration. Thus, the expression of telomerase in aquatic animals is likely not related to longevity but to their ability to regenerate injured tissue.

Transgenic lambda medaka as a new model for germ cell mutagenesis.

To address the need for improved approaches to study mutations transmitted to progeny from mutagen-exposed parents, we evaluated lambda transgenic medaka, a small fish that carries the cII mutation target gene, as a new model for germ cell mutagenesis. Mutations in the cII gene in progeny derived from ethyl-nitrosourea (ENU)-exposed males were readily detected. Frequencies of mutant offspring, proportions of mosaic or whole body mutant offspring, and mutational spectra differed according to germ cell stage exposed to ENU. Postmeiotic germ cells (spermatozoa/late spermatids) generated a higher frequency of mutant offspring (11%) compared to premeiotic germ cells (3.5%). Individuals with cII mutant frequencies (MF) elevated more than threefold above the spontaneous MF (3 x 10(-5)) in the range of 10(-4) to 10(-3) were mosaic mutant offspring, whereas those with MFs approaching 1 x 10(-2) were whole body mutant offspring. Mosaic mutant offspring comprised the majority of mutant offspring derived from postmeiotic germ cells, and unexpectedly, from spermatogonial stem cells. Mutational spectra comprised of two different mutations, but at identical sites were unusual and characteristic of delayed mutations, in which fixation of a second mutation was delayed following fertilization. Delayed mutations and prevalence of mosaic mutant offspring add to growing evidence that implicates germ cells in mediating processes postfertilization that contribute to genomic instability in progeny. This model provides an efficient and sensitive approach to assess germ cell mutations, expands opportunities to increase understanding of fundamental mechanisms of mutagenesis, and provides a means for improved assessment of potential genetic health risks.

Characterization of toxic effects of sediment-associated organic pollutants using the lambda transgenic medaka.

A novel sediment-contact assay using embryos of the transgenic medaka was developed to fully characterize the toxic effects induced by exposure to a mixture of organic pollutants in sediments. Embryos of the lambda transgenic medaka were exposed for 10 days to a clean reference sediment spiked with either the solvent alone, benzo[a]pyrene (B[a]P), or three concentrations (0.3x, 1x, and 2x) of an organic extract (OE) of sediments from the Seine estuary. The 1 x OE-spiked sediment contained concentrations of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls similar to those in field-collected sediment. Exposure to this sediment, but not to the B[a]P-spiked sediment, significantly increased embryo-larval mortality and prevalence of spinal deformities. Mutant frequency at the cII mutation target gene in the liver of 10-week-old medaka was significantly increased following exposure to either B[a]P or the three doses of OE. The predominant OE-induced liver mutations were G:C to T:A transversions, consistent with PAHs being the major contributors to the mutation induction. Liver and gonadal tumors were observed in 35-week-old medaka exposed to either B[a]P (1/25) or to the 1 x OE (1/24). The benefits of medaka as a fish model for toxicological assessment and the benefits of the cII mutation assay for mutation detection combine to provide comprehensive assessment of a wide range of genotoxic and nongenotoxic effects of aquatic pollutants.

Sub-chronic exposure to 1,1-dichloropropene induces frameshift mutations in lambda transgenic medaka.

1,1-Dichloropropene (1,1-DCP) is a contaminant present in both ground and surface waters used as sources for drinking water. Structural similarity to several compounds with known mutagenicity and carcinogenicity, and recent demonstration of mutagenicity in vitro, suggest this compound may be similarly mutagenic in vivo. A transgenic fish model, the lamda transgenic medaka, was used to evaluate the potential mutagenicity of this contaminant in vivo following sub-chronic exposure for 6 weeks. Mutant frequencies of the cII target gene (MF) increased six-fold in the livers of fish exposed to the lowest 1,1-DCP exposure concentration (0.44 mg/L, MF = 18.4 x 10(-5), and increased with each treatment, culminating in a 32-fold induction in fish from the highest 1,1-DCP treatment (16.60 mg/L, MF = 96.3 x 10(-5). Mutations recovered from treated fish showed a distinctive mutational spectrum comprised predominantly of +1 frameshift mutations, induced 166-fold above that of untreated animals. The majority of frameshifts were +1 insertions at thiamine and adenine. These results represent the first evidence of mutagenicity of 1,1-DCP in vivo, and of the highly characteristic spectrum of induced mutations dominated by +1 frameshift mutations. Based upon results from previous in vitro studies, the similar role of glutathione S-transferase (GSTT1-1) in the activation of 1,1-DCP to a mutagen in vivo is also suggested. This study further illustrates the utility of the lamda transgenic medaka as a model for identifying and characterizing potential genetic health risks associated with chemical exposures in the environment.