煤焦沥青诱发大鼠肺癌的实验研究——Ⅱ.形态学观察

本文对煤焦沥青诱发大鼠肺癌过程中的病理形态学所见作了报道。整个过程可以分为三个阶段:1.异物反应阶段;2.异常增生和鳞状化生阶段;3.癌肿发生发展阶段。文中对每一个阶段的病理组织学改变做了详细描述。煤焦沥青诱发的大鼠肺癌的特征如下:1.癌肿全都发生在肺的周边部位;2.绝大多数癌肿的组织类型都是高分化鳞状细胞癌;3.多发性,数个至数十个大小不等的肿块布满全肺;4.癌变各个不同阶段的改变可在同一肺脏中出现;5.转移癌较少见。     

Biomonitoring of aromatic amines and alkylating agents by measuring hemoglobin adducts

Summary Analysis of hemoglobin adducts in blood samples is suitable for the biological monitoring of genotoxic chemicals. The method is specific because the compound to which the individual was exposed is identified. The sensitivity of the method depends on the analytical procedure applied, but is hardly limiting since large amounts of the protein can be obtained. The method provides not only information about the internal exposure to the environmental chemical, but also about the individual's capacity to generate ultimate genotoxic metabolites from it. Since macromolecular damage in blood cells is correlated to that in potential target tissues, this information is relevant to risk assessment, insofar as macromolecular damage produced by a specific chemical can be correlated with the development of tumors.     

Structure-acute toxicity relationship of aromatic hydrocarbons in mice

The structure-acute toxicity relationship of aromatic hydrocarbons was examined in mice. In all test compounds, the acute toxicity was determined under 2 conditions: control LD₅₀ (LD₅₀-cont) and carbon tetrachloride (CCl₄)-pretreated LD₅₀ (LD₅₀-CCl₄). The CCl₄-pretreatment was done in order to evaluate the toxic potency of compound itself without the influence of metabolism. Both log (1/LD₅₀-cont) and log (1/LD₅₀-CCl₄) were functions of the log P, n-octanol/water partition coefficient, i.e., log (1/LD₅₀-cont) = 0.080 log P − 1.532 and log (1/LD₅₀-CCl₄) = −0.040(log P)² + 0.157 log P − 1.373. Both equations were statistically significant (P < 0.01). The ratio of LD₅₀-cont/LD₅₀-CCl₄ indicated that metabolic activation is more evident in hydrophobic compounds than in hydrophilic compounds. The results suggest that hydrophobicity of the aromatic hydrocarbons plays an important role in determining their acute toxicity.     

Cancer risk due to occupational exposure to polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) demonstrate carcinogenic activity in animal models. Although some epidemiologic studies have implicated PAHs as risk factors for human cancer, the evidence reported to date has not been consistent. The purpose of this report is to describe the associations between occupational exposure to PAHs in the workplace and each of 14 types of cancer. A population-based, case-control study was carried out in Montreal to investigate associations between a large variety of environmental and occupational exposures on the one hand, and several types of cancer on the other. A detailed job history was obtained from each subject along with information on a number of potential confounders. Each job history was reviewed by a team of experts, who used this information to construct a corresponding history of occupational exposures. Among the PAH exposures considered were benzo(a)pyrene (B(a)P) and five categories of PAHs defined on the basis of the source material, namely, wood, petroleum, coal, other sources, and any source. Altogether, 3,730 cancer patients and 533 population controls were interviewed and their job exposure histories coded. For each of 14 types of cancer analyzed, three control groups were available: other cancer patients, population controls, and the pooled set of cancer and population controls. The associations between 14 cancer types and 6 PAH exposures were analyzed using logistic regression methods. For most types of cancer evaluated, there was no evidence of excess risk due to PAHs at the levels encountered in the occupations in which PAH exposure has been prevalent in the Montreal area. For a few cancer sites–the esophagus, the pancreas, and the prostate gland–there were suggestions of excess risk; these observations are noteworthy hypotheses for further investigation. For lung cancer, there appeared to be an increased risk due to PAHs among nonsmokers and light smokers, but not among heavy smokers.     

Genotoxicity and physicochemical characteristics of traffic-related ambient particulate matter

Exposure to ambient particulate matter (PM) has been linked to several adverse health effects. Since vehicular traffic is a PM source of growing importance, we sampled total suspended particulate (TSP), PM(10), and PM(2.5) at six urban locations with pronounced differences in traffic intensity. The mutagenicity, DNA-adduct formation, and induction of oxidative DNA damage by the samples were studied as genotoxicological parameters, in relation to polycyclic aromatic hydrocarbon (PAH) levels, elemental composition, and radical-generating capacity (RGC) as chemical characteristics. We found pronounced differences in the genotoxicity and chemical characteristics of PM from the various locations, although we could not establish a correlation between traffic intensity and any of these characteristics for any of the PM size fractions. Therefore, the differences between locations may be due to local sources of PM, other than traffic. The concentration of total (carcinogenic) PAHs correlated positively with RGC, direct and S9-mediated mutagenicity, as well as the induction of DNA adducts and oxidative DNA damage. The interaction between total PAHs and transition metals correlated positively with DNA-adduct formation, particularly from the PM(2.5) fraction. RGC was not associated with one specific PM size fraction, but mutagenicity and DNA reactivity after metabolic activation were relatively high in PM(10) and PM(2.5), when compared with TSP. We conclude that the toxicological characteristics of urban PM samples show pronounced differences, even when PM concentrations at the sample sites are comparable. This implies that emission reduction strategies that take chemical and toxicological characteristics of PM into account may be useful for reducing the health risks associated with PM exposure.     

Rapid hydroxylation of methtryptoline (1-methyltetrahydro-β-carboline) in rat: Identification of metabolites by chiral gas chromatography-mass spectrometry

Summary Racemic methtryptoline (1-methyltetrahydro--carboline) and 5-hydroxymethtryptoline-9-carboxylic acid (6-hydroxy-1-methyltetrahydro--carboline-1-carboxylic acid) were administered intraperitoneally to rats and the components of their urine was subsequently investigated by chiral gas chromatography-mass spectrometry. Methtryptoline rapidly became hydroxylated in the 5- and 6-position and excreted in urine. There was about a ninefold predominance of the S(–) enantiomer over the other in the 5-hydroxylated species, while the 6-hydroxylation produced a small excess of the R(+) enantiomer. About 75% of the injected dose of methtryptoline was recovered in the urine as 5- and 6-hydroxylated compounds during the first 24 h period, demonstrating that hydroxylation represents the major metabolic pathway. Treatment with 6-hydroxymethtryptoline-9-carboxylic acid led to a fivefold increase in the urinary excretion of 5-hydroxymethtryptoline during the first 24 h period with a predominance of the S(–)-enantiomer, indicating a much smaller conversion rate than from methtryptoline. It was concluded that hydroxylation of methtryptoline is a likely pathway for the natural formation of 5-hydroxymethtryptoline.