Characterisation of cytotoxicity and DNA damage induced by the topoisomerase II-directed bisdioxopiperazine anti-cancer agent ICRF-187 (dexrazoxane) in yeast and mammalian cells

Table 2 Hypersensitivity (or resistance) scoring of pMJ1-transformed BY4741 deletion strains towards ICRF-187 and m-AMSA as determined in clonogenic assay using 22.5 hours drug exposure.

Drug	ICRF-187	m-AMSA
Gene deleted
WT	0	0
Nucleotide Excision Repair (NER)
Single Strand Annealing (SSA) Recombination
Anti-Recombination
Δrad1	R	0
Δrad14	0	0
Mismatch Repair (MMR)
Anti-Recombination
Δmsh2	R	0
Δmsh3	0	0
Δmhl1	R	0
Δpms1	R	0
Base Excision Repair (BER)
Δapn1	0	0
Post Replication Repair (PRR)
Δrev1	0	0
Δrev3	0	0
Δrad18	0	+
Δrad6	0	++
Homologous Recombination (HR)
Non-Homologous End Joining (NHEJ)
Δrad50	+	++
Δmre11	+	++
Δxrs2	+	++
Homologous Recombination (HR)
Δrad52	+	++
Δrad51	+	+
Δrad54	+	++
Δrad57	+	++
Δrad55	+	++
Δrad59	0	0
Δdmc1	0	0
Δsae2	+	+
Non-Homologous End Joining (NHEJ)
Δyku70	+	0
Δyku80	0	0
DNA Damage Checkpoints
Δtel1	0	0
Δrad9	0	0
Δmec3	0	0
Δddc1	0	0
Δrad17	0	0
Δchk1	0	0
ABC Transporters (Yeast MDR1 homologous)
Δatr1	0	0
Δpdr5	+	0
Δyor1	0	0
Ubiquitin conjugation / hydrolysis
Δubc4	0	0
Δubc13	0	0
Δdoa4	0	R
Δqri8	0	0
Ribonucleotide-reductase regulation
Δrnr3	0	0
Δsml1	0	0

R: Cells are more than a 1/2 log resistant at any drug concentration.
0: Cells are no more than a 1/2 log resistant and no more than a 1/2 log hypersensitive at any drug concentration.
+: Cells are at least a 1/2 log but no more than 2 log hypersensitive at any concentration.
++: Cells are more than 2 log hypersensitive at any concentration.
Hypersensitivity (resistance) was graduated as follows