559
560
1. IARC WHO. Asbestos (chrysotile, amosite, crocidolite, tremolite, actinolite, and anthophyllite).
561
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans A Review of Human
562
Carcinogens; Part C: Arsenic, Metals, Fibres, and Dusts. Lyon, France, 2012; 219-309.
563
564
565
2. Thives LP, Ghisi E, Thives Junior JJ, Vieira AS. Is asbestos still a problem in the world? A
current review. J Environ Manage. 2022; 319: 115716.
3. Jiang Z, Chen J, Chen J, et al. Mortality due to respiratory system disease and lung cancer
566
among female workers exposed to chrysotile in Eastern China: A cross-sectional study. Front
567
Oncol. 2022; 12: 928839.
568
Fo
4. Hodgson JT, McElvenny DM, Darnton AJ, Price MJ, Peto J. The expected burden of
569
mesothelioma mortality in Great Britain from 2002 to 2050. Br J Cancer. 2005; 92: 587-93.
570
5. Jiang L, Nagai H, Ohara H, et al. Characteristics and modifying factors of asbestos-induced
572
6. Jiang L, Akatsuka S, Nagai H, et al. Iron overload signature in chrysotile-induced malignant
mesothelioma. J Pathol. 2012; 228: 366-77.
iew
573
oxidative DNA damage. Cancer Sci. 2008; 99: 2142-51.
ev
571
rR
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Cancer Science
574
7. Toyokuni S. Mechanisms of asbestos-induced carcinogenesis. Nagoya J Med Sci. 2009; 71: 1-10.
575
8. Toyokuni S. Iron addiction with ferroptosis-resistance in asbestos-induced mesothelial
576
carcinogenesis: Toward the era of mesothelioma prevention. Free Radic Biol Med. 2019; 133:
577
206-15.
578
579
580
581
9. Yoshida R. Hereditary breast and ovarian cancer (HBOC): review of its molecular
characteristics, screening, treatment, and prognosis. Breast Cancer. 2021; 28: 1167-80.
10. Deng CX. BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer
evolution. Nucleic Acids Res. 2006; 34: 1416-26.
582
11. Betti M, Casalone E, Ferrante D, et al. Germline mutations in DNA repair genes predispose
583
asbestos-exposed patients to malignant pleural mesothelioma. Cancer Lett. 2017; 405: 38-45.
584
12. Jensen DE, Proctor M, Marquis ST, et al. BAP1: a novel ubiquitin hydrolase which binds to the
CAS Editorial office (Email: cancerscience@wiley.com)
Cancer Science
Y LUO et al. 26
585
BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene. 1998;
586
16: 1097-112.
587
588
589
590
591
13. Testa JR, Cheung M, Pei J, et al. Germline BAP1 mutations predispose to malignant
mesothelioma. Nat Genet. 2011; 43: 1022-5.
14. Evers B, Jonkers J. Mouse models of BRCA1 and BRCA2 deficiency: past lessons, current
understanding and future prospects. Oncogene. 2006; 25: 5885-97.
15. Nakamura Y, Kubota J, Nishimura Y, et al. Brca1(L63X) (/+) rat is a novel model of human
592
BRCA1 deficiency displaying susceptibility to radiation-induced mammary cancer. Cancer Sci.
593
2022; 113: 3362-75.
594
16. Toyokuni S, Kong Y, Cheng Z, et al. Carcinogenesis as Side Effects of Iron and Oxygen
595
Utilization: From the Unveiled Truth toward Ultimate Bioengineering. Cancers (Basel). 2020;
596
12: 3320.
rR
597
Fo
17. Kong Y, Akatsuka S, Motooka Y, et al. BRCA1 haploinsufficiency promotes chromosomal
598
amplification under Fenton reaction-based carcinogenesis through ferroptosis-resistance.
599
Redox Biol. 2022; 54: 102356.
601
602
18. Toyokuni S, Kong Y, Zheng H, Maeda Y, Motooka Y, Akatsuka S. Iron as spirit of life to share
iew
600
ev
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Page 26 of 38
under monopoly. J Clin Biochem Nutr. 2022; 71: 78-88.
19. Nagai H, Okazaki Y, Chew SH, Misawa N, Yasui H, Toyokuni S. Deferasirox induces
603
mesenchymal-epithelial transition in crocidolite-induced mesothelial carcinogenesis in rats.
604
Cancer Prev Res. 2013; 6: 1222-30.
605
20. Ohara Y, Chew SH, Shibata T, Okazaki Y, Yamashita K, Toyokuni S. Phlebotomy as a
606
preventive measure for crocidolite-induced mesothelioma in male rats. Cancer Sci. 2018; 109:
607
330-9.
608
609
610
611
612
21. Jiang L, Yamashita Y, Toyokuni S. A novel method for efficient collection of normal
mesothelial cells in vivo. J Clin Biochem Nutr. 2010; 46: 265-8.
22. Oury TD, Sporn TA, Roggli VL (Eds). Pathology of Asbestos-Associated Diseases, Third
edition. Berlin/Heidelberg: Springer, 2014.
23. Kajiyama H, Kikkawa F, Maeda O, Suzuki T, Ino K, Mizutani S. Increased expression of
CAS Editorial office (Email: cancerscience@wiley.com)
Page 27 of 38
Y LUO et al. 27
613
dipeptidyl peptidase IV in human mesothelial cells by malignant ascites from ovarian
614
carcinoma patients. Oncology-Basel. 2002; 63: 158-65.
615
24. Cheng Z, Akatsuka S, Li GH, Mori K, Takahashi T, Toyokuni S. Ferroptosis resistance
616
determines high susceptibility of murine A/J strain to iron-induced renal carcinogenesis.
617
Cancer Sci. 2022; 113: 65-78.
618
25. Nagai H, Okazaki Y, Chew S, et al. Diameter of multi-walled carbon nanotubes is a critical
619
factor in mesothelial injury and subsequent carcinogenesis. Proc Natl Acad Sci U S A. 2011;
620
108: E1330-8.
621
622
623
624
26. Yue L, Luo Y, Jiang L, Sekido Y, Toyokuni S. PCBP2 knockdown promotes ferroptosis in
malignant mesothelioma. Pathol Int. 2022; 72: 242-51.
27. Yoshida K, Miki Y. Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription,
Fo
and cell cycle in response to DNA damage. Cancer Sci. 2004; 95: 866-71.
rR
625
28. Illei PB, Rusch VW, Zakowski MF, Ladanyi M. Homozygous deletion of CDKN2A and
626
codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural
627
mesotheliomas. Clin Cancer Res. 2003; 9: 2108-13.
29. Lopez-Rios F, Chuai S, Flores R, et al. Global gene expression profiling of pleural
iew
628
ev
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Cancer Science
629
mesotheliomas: overexpression of aurora kinases and P16/CDKN2A deletion as prognostic
630
factors and critical evaluation of microarray-based prognostic prediction. Cancer Res. 2006; 66:
631
2970-9.
632
633
30. Kuo LJ, Yang LX. Gamma-H2AX - a novel biomarker for DNA double-strand breaks. In Vivo.
2008; 22: 305-9.
634
31. Harington JS, Miller K, Macnab G. Hemolysis by asbestos. Environ Res. 1971; 4: 95-117.
635
32. Nagai H, Ishihara T, Lee WH, et al. Asbestos surface provides a niche for oxidative
636
637
modification. Cancer Sci. 2011; 102: 2118-25.
33. Toyokuni S, Tanaka T, Hattori Y, et al. Quantitative immunohistochemical determination of 8-
638
hydroxy-2'-deoxyguanosine by a monoclonal antibody N45.1: its application to ferric
639
nitrilotriacetate-induced renal carcinogenesis model. Lab Invest. 1997; 76: 365-74.
640
34. Zheng H, Jiang L, Tsuduki T, Conrad M, Toyokuni S. Embryonal erythropoiesis and aging
CAS Editorial office (Email: cancerscience@wiley.com)
Cancer Science
Y LUO et al. 28
641
642
643
644
exploit ferroptosis. Redox Biol. 2021; 48: 102175.
35. Stockwell BR. Ferroptosis turns 10: Emerging mechanisms, physiological functions, and
therapeutic applications. Cell. 2022; 185: 2401-21.
36. Ito F, Yanatori I, Maeda Y, et al. Asbestos conceives Fe(II)-dependent mutagenic stromal
645
milieu through ceaseless macrophage ferroptosis and beta-catenin induction in mesothelium.
646
Redox Biol. 2020; 36: 101616.
647
37. Ito F, Kato K, Yanatori I, Murohara T, Toyokuni S. Ferroptosis-dependent extracellular
648
vesicles from macrophage contribute to asbestos-induced mesothelial carcinogenesis through
649
loading ferritin. Redox Biol. 2021; 47: 102174.
650
651
652
39. Toyokuni S, Yanatori I, Kong Y, Zheng H, Motooka Y, Jiang L. Ferroptosis at the crossroads of
infection, aging and cancer. Cancer Sci. 2020; 111: 2665-71.
40. Toyokuni S, Kong Y, Zheng H, Maeda Y, Katabuchi M, Motooka Y. Three-dimensional
ev
654
Metallomics Res. 2021; 1: 14-21.
rR
653
38. Toyokuni S, Ito F, Motooka Y. Role of ferroptosis in nanofiber-induced carcinogenesis.
Fo
655
regulation of ferroptosis at the intersection of iron, sulfur and oxygen executing scrap and
656
build toward evolution. Antioxid Redox Signal. 2022. doi: 10.1089/ars.2022.0142.
657
iew
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
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43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Page 28 of 38
41. Nagai H, Toyokuni S. Differences and similarities between carbon nanotubes and asbestos
658
fibers during mesothelial carcinogenesis: shedding light on fiber entry mechanism. Cancer Sci.
659
2012; 103: 1378-90.
660
661
662
663
664
665
666
667
668
42. Nagai H, Chew S, Okazaki Y, et al. Metamorphosis of mesothelial cells wtih active horizontal
motility in tissue culture. Sci Rep. 2013; 3: 1144.
43. Toyokuni S, Kong Y, Zheng H, et al. Double-edged Sword Role of Iron-loaded Ferritin in
Extracellular Vesicles. J Cancer Prev. 2021; 26: 244-9.
44. Kawabata H. Transferrin and transferrin receptors update. Free Radic Biol Med. 2019; 133: 4654.
45. Stockwell BR, Friedmann Angeli JP, Bayir H, et al. Ferroptosis: A Regulated Cell Death Nexus
Linking Metabolism, Redox Biology, and Disease. Cell. 2017; 171: 273-85.
46. Toyokuni S, Okamoto K, Yodoi J, Hiai H. Persistent oxidative stress in cancer. FEBS Lett. 1995;
CAS Editorial office (Email: cancerscience@wiley.com)
Page 29 of 38
Y LUO et al. 29
669
670
671
672
673
674
675
676
677
678
679
680
683
48. Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of
nonapoptotic cell death. Cell. 2012; 149: 1060-72.
49. Friedmann Angeli JP, Schneider M, Proneth B, et al. Inactivation of the ferroptosis regulator
Gpx4 triggers acute renal failure in mice. Nat Cell Biol. 2014; 16: 1180-91.
50. Toyokuni S, Miyake N, Hiai H, et al. The monoclonal antibody specific for the 4-hydroxy-2nonenal histidine adduct. FEBS Lett. 1995; 359: 189-91.
51. Ozeki M, Miyagawa-Hayashino A, Akatsuka S, et al. Susceptibility of actin to modification by
4-hydroxy-2-nonenal. J Chromatogr B Analyt Technol Biomed Life Sci. 2005; 827: 119-26.
52. Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by
GPX4. Cell. 2014; 156: 317-31.
53. Jiang L, Kon N, Li T, et al. Ferroptosis as a p53-mediated activity during tumour suppression.
Nature. 2015; 520: 57-62.
iew
684
suppression. Nat Cell Biol. 2018; 20: 1181-92.
ev
682
47. Zhang Y, Shi J, Liu X, et al. BAP1 links metabolic regulation of ferroptosis to tumour
rR
681
358: 1-3.
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Cancer Science
Table 1 Summary of malignant mesotheliomas (MMs) in asbestos-injected rats
Brca1 Mut
Wild-type
Male
Female
Male
Female
Crocidolite
6/10(60.0%)
4/9(44.4%)
6/8(75.0%)
6/8(75.0%)
Chrysotile
7/9(77.8%)
9/9(100.0%)
8/10(80.0%)
7/11(63.6%)
Control
0/10
0/10
0/10
0/10
Brca1 Mut, Brca1 mutant (L63X/+). Refer to text for details.
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Figure 1
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Figure 3
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Figure 5
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