Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.
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评估低剂量暴露于环境中化学混合物的致癌潜力：未来的挑战。
DOI：
10.1093/carcin/bgv039
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发表时间：
2015-06
期刊：
影响因子：
4.7
通讯作者：
Hu Z
中科院分区：
文献类型：
--
作者：
Goodson WH 3rd;Lowe L;Carpenter DO;Gilbertson M;Manaf Ali A;Lopez de Cerain Salsamendi A;Lasfar A;Carnero A;Azqueta A;Amedei A;Charles AK;Collins AR;Ward A;Salzberg AC;Colacci A;Olsen AK;Berg A;Barclay BJ;Zhou BP;Blanco-Aparicio C;Baglole CJ;Dong C;Mondello C;Hsu CW;Naus CC;Yedjou C;Curran CS;Laird DW;Koch DC;Carlin DJ;Felsher DW;Roy D;Brown DG;Ratovitski E;Ryan EP;Corsini E;Rojas E;Moon EY;Laconi E;Marongiu F;Al-Mulla F;Chiaradonna F;Darroudi F;Martin FL;Van Schooten FJ;Goldberg GS;Wagemaker G;Nangami GN;Calaf GM;Williams G;Wolf GT;Koppen G;Brunborg G;Lyerly HK;Krishnan H;Ab Hamid H;Yasaei H;Sone H;Kondoh H;Salem HK;Hsu HY;Park HH;Koturbash I;Miousse IR;Scovassi AI;Klaunig JE;Vondráček J;Raju J;Roman J;Wise JP Sr;Whitfield JR;Woodrick J;Christopher JA;Ochieng J;Martinez-Leal JF;Weisz J;Kravchenko J;Sun J;Prudhomme KR;Narayanan KB;Cohen-Solal KA;Moorwood K;Gonzalez L;Soucek L;Jian L;D'Abronzo LS;Lin LT;Li L;Gulliver L;McCawley LJ;Memeo L;Vermeulen L;Leyns L;Zhang L;Valverde M;Khatami M;Romano MF;Chapellier M;Williams MA;Wade M;Manjili MH;Lleonart ME;Xia M;Gonzalez MJ;Karamouzis MV;Kirsch-Volders M;Vaccari M;Kuemmerle NB;Singh N;Cruickshanks N;Kleinstreuer N;van Larebeke N;Ahmed N;Ogunkua O;Krishnakumar PK;Vadgama P;Marignani PA;Ghosh PM;Ostrosky-Wegman P;Thompson PA;Dent P;Heneberg P;Darbre P;Sing Leung P;Nangia-Makker P;Cheng QS;Robey RB;Al-Temaimi R;Roy R;Andrade-Vieira R;Sinha RK;Mehta R;Vento R;Di Fiore R;Ponce-Cusi R;Dornetshuber-Fleiss R;Nahta R;Castellino RC;Palorini R;Abd Hamid R;Langie SA;Eltom SE;Brooks SA;Ryeom S;Wise SS;Bay SN;Harris SA;Papagerakis S;Romano S;Pavanello S;Eriksson S;Forte S;Casey SC;Luanpitpong S;Lee TJ;Otsuki T;Chen T;Massfelder T;Sanderson T;Guarnieri T;Hultman T;Dormoy V;Odero-Marah V;Sabbisetti V;Maguer-Satta V;Rathmell WK;Engström W;Decker WK;Bisson WH;Rojanasakul Y;Luqmani Y;Chen Z;Hu Z
低剂量暴露于被认为单独安全的常见环境化学品可能会联合起来诱发致癌作用，从而导致癌症的发生。这种风险可能被当前的监管做法所忽视，需要大力调查。生活方式因素是全球癌症发病率的重要原因，但世界卫生组织和国际癌症研究机构（IARC）的可靠估计表明，有毒环境暴露导致的癌症比例在7%至19%之间。为了探索低剂量暴露于环境中的化学品混合物可能结合起来导致环境致癌的假设，我们审查了11种癌症的标志表型，每个区域的多个优先目标点以及所有目标的原型化学干扰物，这包括剂量反应特性，低剂量效应的证据和所有目标和化学品的交叉标志效应。总共审查了85种化学品的致癌作用关键途径/机制。发现只有15%（13/85）有剂量反应阈值的证据，而59%（50/85）表现出低剂量效应。其余26%（22/85）未发现剂量反应信息。我们的分析表明，单个（非致癌）化学品作用于不同途径的累积效应，以及各种相关系统，器官，组织和细胞可能会共同产生致癌协同作用。在进一步推进这一假设的优点之前，需要严格开展关于致癌作用的额外基础研究和侧重于化学混合物低剂量效应的研究。然而，世界卫生组织国际化学品安全方案“行动模式”框架的结构应重新审查，因为它具有与我们目前对癌症生物学的理解不完全一致的内在弱点。
Low-dose exposures to common environmental chemicals that are deemed safe individually may be combining to instigate carcinogenesis, thereby contributing to the incidence of cancer. This risk may be overlooked by current regulatory practices and needs to be vigorously investigated. Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
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DOI：
10.1152/ajplung.00165.2013
发表时间：
2013-11-01
影响因子：
4.9
作者：
Agarwal, Amit R.;Yin, Fei;Cadenas, Enrique
通讯作者：
Cadenas, Enrique
DOI：
10.1073/pnas.1010386107
发表时间：
2010-11-23
影响因子：
11.1
作者：
Allard, Patrick;Colaiacovo, Monica P.
通讯作者：
Colaiacovo, Monica P.
影响因子：
6.1
作者：
Andrysik, Zdenek;Prochazkova, Jirina;Vondracek, Jan
通讯作者：
Vondracek, Jan
影响因子：
3.3
作者：
Ahmad, Israr;Kumar, Ashutosh;Singh, Chetna
通讯作者：
Singh, Chetna
影响因子：
4.3
作者：
Ansari, Kausar M.;Das, Mukul
通讯作者：
Das, Mukul