Table B.6.

Temporality concordance table

Model (concentration)	MIE Unknown	KE1 In utero induction of chromosomal translocations	KE2 Differentiation blockage	KE3 Clonal expansion	AO Childhood leukaemia
Conditional activation of E2A‐PBX1 in the B cell compartment of micea		+	+	+	ALL development (similar to human E2A‐PBX1+ leukaemias)
Transplantation of TEL‐AML1 transduced human cord blood cells into NOD/SCID miceb			+	+ Mice exhibited features of preleukaemic phase of pre‐B cell ALLb	‐
Human peripheral lymphocytes exposed to 0.1–10 μg/mL isofenphos for 1 h	Dose‐dependent damage to chromosomal DNA could lead to genomic instability and leukaemogenesisc	+	‐	‐	‐
Human K562 cells exposed to 0.1 μM of diazinon	Hypermethylation of genes involved in cell cycle arrest (cyclin‐dependent kinase inhibitor 1A and CDKN1C) as well as tumour suppressor genes (p53 and PTEN)d	‐	‐	‐	‐
1–100 μM chlorpyrifos for up to 24 h	Dose‐ and time‐dependent double‐strand DNA breaks in HSCs (and MLL rearrangements)e	+	‐	‐	‐
Human T‐cell leukaemia Jurkat cells exposed to methyl‐pyrazole insecticides for 1 h	Increased double DNA breaks (possibly due to oxidative stress)f	‐	‐	‐	‐
CEM x 174 cell line, (a hybrid of human T and B cells), exposed to 50 μM heptachlor, chlordane or toxaphene for 24–36 h	Decrease in levels of the tumour suppressors p53 and Rbg , h	?	‐	‐	‐
Human peripheral lymphocytes exposed to a commercial fungicide karathane (dinocap) at 20 μg/mL for 24 h		Increased chromosomal aberrations, formation of sister chromatid exchanges and decreased mitotic indexi	‐	‐	‐
Studies on the Kasumi‐1 cell line, which harbours an AML1–ETO translocation			The differentiation block induced by AML1–ETO is due in part to its ability to physically bind to and inactivate the master myeloid transcription factor PU.1j	‐	‐

^aA conditional E2A‐PBX1 allele was engineered to recombine human PBX1a cDNA into the mouse E2A locus to create an E2A‐PBX1 fusion gene (Duque‐Afonso et al., 2015).

^bHong D, Gupta R, Ancliff P, Atzberger A, Brown J, Soneji S, Green J, Colman S, Piacibello W, Buckle V, Tsuzuki S, Greaves M and Enver T, 2008. Initiating and cancer‐propagating cells in TEL‐AML1‐associated childhood leukemia. Science, 319, 336–339.

^cWilliams RD, Boros LG, Kolanko CJ, Jackman SM and Eggers TR, 2004. Chromosomal aberrations in human lymphocytes exposed to the anticholinesterase pesticide isofenphos with mechanisms of leukemogenesis. Leukemia Research, 28, 947–958.

^dZhang X, Wallace AD, Du P, Lin S, Baccarelli AA, Jiang H, Jafari N, Zheng Y, Xie H, Soares MB, Kibbe WA and Hou L, 2012. Genome‐wide study of DNA methylation alterations in response to diazinon exposure in vitro. Environmental Toxicology and Pharmacology, 34, 959–968.

^eLu C, Liu X, Liu C, Wang J, Li C, Liu Q, Li Y, Li S, Sun S, Yan J and Shao J, 2015. Chlorpyrifos Induces MLL Translocations Through Caspase 3‐Dependent Genomic Instability and Topoisomerase II Inhibition in Human Fetal Liver Hematopoietic Stem Cells. Toxicological Sciences, 147, 588–606.

^fGraillot V, Tomasetig F, Cravedi JP and Audebert M, 2012. Evidence of the in vitro genotoxicity of methyl‐pyrazole pesticides in human cells. Mutation Research‐Genetic Toxicol Environ Mutag, 748, 8–16.

^gRought SE, Yau PM, Chuang LF, Doi RH and Chuang RY, 1999. Effect of the chlorinated hydrocarbons heptachlor, chlordane, and toxaphene on retinoblastoma tumor suppressor in human lymphocytes. Toxicology Letters, 104, 127–135.

^hRought SE, Yau PM, Schnier JB, Chuang LF and Chuang RY, 1998. The effect of heptachlor, a chlorinated hydrocarbon insecticide on p53 tumor suppressor in human lymphocytes. Toxicology Letters, 94, 29–36.

ⁱCelik M, Unal F, Yuzbasioglu D, Ergun MA, Arslan O and Kasap R, 2005. In vitro effect of karathane LC (dinocap) on human lymphocytes. Mutagenesis, 20, 101–104.

^jVangala RK, Heiss‐Neumann MS, Rangatia JS, Singh SM, Schoch C, Tenen DG, Hiddemann W and Behre G, 2003. The myeloid master regulator transcription factor PU.1 is inactivated by AML1–ETO in t(8;21) myeloid leukemia. Blood, 101, 270–277.