Supplemental Material for Zeiss et al., 2019

S1 Fig 1: Renal scores across all 10 CC strains.
Means and standard error at each weekly time point are shown for each strain,
with a vertical gray line delineating acute (A; 6 weeks) and chronic (C; 12
week) time points. Females are shown on the top panel and males beneath. The
majority of doxorubicin-treated animals (red) demonstrate renal injury
(increased scores) over time compared to age matched vehicle treated controls
(blue). Strains with p values <0.05
for treatment effect (black asterisk), treatment*sex (gray asterisk), and
treatment*timepoint (white asterisk) interactions are indicated with asterisks
located above each strain name. Strain 40 is very susceptible, with most
doxorubicin-treated animals dying before the end of the study.

S2 Fig 2: Renal, splenic and testicular
pathology in doxorubicin -treated mice. Animals with severe renal pathology (A)
experienced diffuse tubuloglomerular injury. Glomerular pathology was
characterized by increased mesangial matrix, proliferation of parietal
epithelium of Bowman’s capsule (B), and segmental necrosis or fibrosis. Tubular
injury was accompanied by interstitial lympho-histiocytic inflammation (arrow,
C), tubular epithelial atrophy (B, C) and accumulation of hyaline casts (C).
Splenic pathology varied from marked extramedullary hematopoiesis (asterisk, D)
to collapse of red pulp and splenic atrophy (asterisk, E). White pulp remained
intact. Testicular atrophy was characterized by loss of the entire
spermatogenic series (F).
Hematoxylin
and eosin, Bar = 100µm (A); 20µm (B), 50µm (C, F), 1mm (D, E)

S3 Fig 3: Hematologic parameters: Red blood cell counts (RBC, A)
decreased at the acute time point (orange) in almost all strains, except CC051.
Most strains recovered by the chronic time point (blue), but some strains
(CC001, CC011, CC042) still had decreased RBC. Red blood cell distribution
width (RDW, B, an indicator of increased red cell diameter characteristic of
regeneration) was increased in all strains at the acute time point. Most
strains had recovered by the chronic time point, except for CC032 and CC042. We
found that DOX did not cause neutropenia (or lymphopenia, data not shown) at
either the acute (orange) or chronic (blue) time points (C). Many strains
(CC010, CC040, CC041) showed increased neutrophil counts at the acute time
point. This increase persisted at the chronic time point in some strains
(CC010, CC032, CC041). Some strains (CC011, CC040) showed increased platelets
at the acute time point (D), with other strains (CC001, CC019, CC032, CC042)
showed sex-specific increases. This was accompanied by histologic evidence of
marked splenic extramedullary hematopoeisis. Most strains had recovered by the
chronic time point.

Supporting Table 2: Statistical analysis of semi-quantitative renal
scoring.