An examination of the time course from human dietary exposure to polycyclic aromatic hydrocarbons to urinary elimination of 1-hydroxypyrene.

The significance of diet as an exposure route for polycyclic aromatic hydrocarbons (PAHs) and the associated kinetics of urinary 1-hydroxypyrene (1-OHPY) elimination were examined through a controlled human exposure study. Results showed that a 100 to 250-fold increase in a dietary benzo(a)pyrene (BaP) dose paralleled a four to 12-fold increase in urinary 1-OHPy elimination. Mean elimination rates during minimal exposure periods ranged from 6 to 17 ng/h whereas peak elimination rates of 60 to 189 ng/h were seen after a meal high in PAHs. A biexponential model fitted to a limited number of urinary 1-OHPY elimination points gave mean kinetic parameter estimates for t1/2 of 4.4 hours and tmax of 6.3 hours. It is concluded that dietary exposure to PAHs is potentially as substantial as some occupational exposures and therefore requires consideration in studies of exposure to PAHs. The dietary control strategies and the kinetic parameters defined in this investigation provide data for the control of this exposure route when examining other sources of exposure.     

Breath ammonia depletion and its relevance to acidic aerosol exposure studies.

It is thought that gaseous ammonia in breath neutralizes acidic air pollution and thereby potentially mitigates the pulmonary effects of pollution. The efficacy of breath ammonia depletion methods reported in recent acid aerosol exposure-health response studies was investigated. Fourteen subjects (21 to 54 y of age) performed one or more of the following hygiene maneuvers: (a) acidic oral rinse (pH 2.5); (b) tooth brushing, followed by acidic oral rinse; (c) tooth brushing, followed by distilled water rinse; and (d) distilled water rinse. Initial ammonia levels ranged from 120 to 1,280 ppb (147-1,570 micrograms/m3). Acidic rinsing resulted in an immediate 90% reduction in exhaled ammonia in all subjects, and a return to 50% of baseline levels occurred within 1 h. Depletion that resulted from tooth brushing or distilled water alone was not significant. It was concluded that acidic oral rinsing is an effective method of reducing airway ammonia, but repeated oral rinsing may be required to maintain consistent, low-breath-ammonia conditions during acid aerosol exposure studies.     

乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。     

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.      

An assessment of a urinary biomarker for total human environmental exposure to benzo[a]pyrene

Urinary banzo[a]pyrene (BaP) metabolite levels were compared to human environmental exposure to BaP through inhalation and dietary ingestion to assess the predictive validity of the exposure biomarker. These measurements were made for 14 adult volunteers over 14 consecutive days, once during summer/fall, again during winter periods. Based on personal air monitoring, median potential inhalation doses of 11.0 and 2.3 ng/day were estimated for the winter and summer/fall studies, respectively. A median potential ingested dose of 176 ng/day, estimated from duplicate plate sampling, exceeded inhalation by 6-and 122-fold for the winter and summer/fall studies, respectively. Total urinary BaP metabolites were measured using a published reverse metabolism (BaP) method of analysis. Median rates of urinary BaP metabolite elimination for the winter and summer/fall studies were 121 and 129 ng/day, respectively. The changes in inhaled and ingested potential doses were regressed on the change in urinary metabolite elimination from week 1 to week 2 to test the predictive validity of the biomarker measurement. The regression was statistically significant (r = 0.620, p = 0.015, n = 25) when body weight was included and two extreme values were removed. Consistent with the exposure measurements showing diet as the dominant route of exposure, most of the variation in urinary metabolite elimination was explained by the ingested dose. It is concluded that the measurement of urinary BaP by reverse metabolism is qualitative and of marginal predictive validity as an exposure biomarker due to the method's low recoveries and the large unexplained variance.     

Quantification of children's hand and mouthing activities through a videotaping methodology.

A videotaping methodology has been developed for use in quantifying the types and frequencies of children's hand and mouthing activities that could lead to exposure to environmental pollutants via dermal and ingestion pathways. Twenty children in day care, ages 3-6 years and 10 children in residences, ages 2-5 years, were videotaped during their waking hours for 1 day. Parents of each child completed questionnaires for the purpose of evaluating the accuracy of parental reports of hand-to-mouth rates. Videotapes were translated as quantifiable activities by two trained observers whose reporting reliability was checked throughout the investigation. Results determined that reliability of the videotaping method was very good, even over a year post-training. From videotape data, the average hand-to-mouth frequency rate was determined to be 9.5 contacts/h. These values are considerably higher than the current default value of 1.56 contacts/h under consideration by the EPA.     

The EL sampler: a press sampler for the quantitative estimation of dermal exposure to pesticides in housedust.

Indirect sampling techniques to estimate dermal exposure to pesticides on housedust-laden indoor surfaces should demonstrate collection efficiencies, for both particles and pesticide residues, which are similar to those that would adhere to the human skin. A spring-loaded press sampler has been developed that approximated the particle- and pesticide-collection efficiencies of a hand press of a human participant. Particle-collection efficiencies for the hand press and EL sampler, using housedust sieved to <250 microm in diameter, indicated that both sampling techniques collected similar particle fractions over the range of particle sizes. Pesticide-collection efficiencies measured on the participants hand (seven paired tests) were 42+/-7% atrazine, 29+/-8% diazinon, 43+/-8% malathion and 21+/-5% chlorpyrifos. The EL sampler collected 35+/-5%, 31+/-3%, 32+/-5% and 18+/-3% respectively. The collection efficiencies of the two sampling techniques were highly correlated for atrazine, diazinon, and chlorpyrifos (correlation coefficient=0.840, 0.815, and 0.706), but not for malathion (correlation coefficient=0.086).     

Multigenic control of skin tumor susceptibility in SENCARA/Pt mice

Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty- one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.