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Allergic contact sensitizing chemicals as environmental carcinogens.

機(jī)譯：過(guò)敏性接觸致敏化學(xué)品為環(huán)境致癌物。

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Chemicals that were bioassayed by the National Toxicology Program (NTP) and that also produce allergic dermatitis (ACD) in humans were evaluated for their tumorigenic characteristics. The impetus for the study was that most contact sensitizers, i.e., those that produce ACD, and genotoxic carcinogens are chemically similar in that they are electrophilic, thereby producing adducts on macromolecules including protein and DNA. This similarity in chemical behavior suggests that many contact sensitizers might be environmental carcinogens. All of the published NTP bioassays by early 1996 that had both genotoxicity and carcinogenicity studies were included in this analysis. The NTP chemicals had been chosen for bioassay without regard to their ability to produce ACD. Of the 209 chemicals that were bioassayed, there were 36 (17%) that were known to be human contact sensitizers; about half of these were positive on tumor bioassays. The contact sensitizers differed from the NTP sample as a whole by having a proportionately larger number of nongenotoxic chemicals by the Ames Salmonella assay, presumably because more of them were selected on the basis of widespread usage rather than structural resemblance to known carcinogens. Compared to the nongenotoxic chemicals, the genotoxics were stronger carcinogens in that they had a higher incidence of positive tumor bioassays, with twice the number of organs in which tumors were induced. The nongenotoxic chemicals had a preference for tumor induction in parenchymal tissues in contrast to epithelial tissues. The contact sensitizers showed essentially the same characteristics as the whole NTP sample when stratified according to genotoxicity. Judging by the chemicals that were chosen primarily for their widespread use rather than for their structural resemblance to carcinogens, the addition of a test for contact sensitization to the Ames test as a screening tool would increase the tumorigenic detection efficiency by about 40% because of the nongenotoxic tumorigens. A ballpark estimate suggests that there could be several thousand contact sensitizers for humans in commercial use that are rodent tumorigens.
機(jī)譯：對(duì)通過(guò)國(guó)家毒理學(xué)計(jì)劃（NTP）進(jìn)行生物分析并且還會(huì)在人體內(nèi)產(chǎn)生過(guò)敏性皮炎（ACD）的化學(xué)藥品的致癌特性進(jìn)行了評(píng)估。該研究的推動(dòng)力是大多數(shù)接觸敏化劑，即產(chǎn)生ACD的那些和遺傳毒性致癌物在化學(xué)上相似，因?yàn)樗鼈兪怯H電的，從而在大分子上產(chǎn)生加合物，包括蛋白質(zhì)和DNA?；瘜W(xué)行為的相似性表明，許多接觸敏化劑可能是環(huán)境致癌物。到1996年初，所有已發(fā)表的同時(shí)具有遺傳毒性和致癌性研究的NTP生物測(cè)定法都包括在該分析中。選擇NTP化學(xué)品進(jìn)行生物測(cè)定時(shí)，無(wú)需考慮產(chǎn)生ACD的能力。經(jīng)過(guò)生物測(cè)定的209種化學(xué)藥品中，有36種（17％）被稱為人類接觸敏化劑。其中約一半在腫瘤生物測(cè)定中呈陽(yáng)性。接觸敏化劑與整個(gè)NTP樣品的不同之處在于，通過(guò)Ames沙門氏菌測(cè)定法具有一定比例的大量非遺傳毒性化學(xué)物質(zhì)，大概是因?yàn)樗鼈兊倪x擇更多是基于廣泛的用途而不是與已知致癌物的結(jié)構(gòu)相似。與非遺傳毒性化學(xué)藥品相比，遺傳毒性更強(qiáng)的致癌物，因?yàn)樗鼈兙哂休^高的陽(yáng)性腫瘤生物檢測(cè)陽(yáng)性率，其誘發(fā)腫瘤的器官數(shù)量是其兩倍。與上皮組織相比，非遺傳毒性化學(xué)物質(zhì)優(yōu)先在實(shí)質(zhì)組織中誘導(dǎo)腫瘤。根據(jù)基因毒性分層時(shí)，接觸敏化劑顯示出與整個(gè)NTP樣品基本相同的特性。從主要是由于其廣泛用途而不是與致癌物的結(jié)構(gòu)相似而選擇的化學(xué)藥品來(lái)看，在Ames試驗(yàn)中添加接觸敏化試驗(yàn)作為篩查工具將使致癌性檢測(cè)效率提高約40％，因?yàn)榉沁z傳毒性腫瘤。粗略估計(jì)表明，可能有成千上萬(wàn)種用于人類的接觸性敏化劑是嚙齒動(dòng)物的致癌物。

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