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AOM/DSS-Induced Colorectal Cancer Model Service

Fig 1: AOM/DSS-Induced Colorectal Cancer Model preclinical research.

The AOM/DSS-induced colorectal cancer model is the most widely adopted preclinical system for recapitulating inflammation-driven colorectal tumorigenesis, combining a single carcinogen injection with cycles of colitis induction to generate tumors that closely mirror the human colitis-associated cancer sequence. Alfa Cytology delivers a fully managed AOM/DSS-induced colorectal cancer model service, covering study design, model induction, longitudinal monitoring, and downstream histopathological and molecular readouts, so that research teams can advance their drug discovery programs with confidence.

Overview of AOM/DSS-Induced Colorectal Cancer Model

Colorectal cancer arising on a background of chronic intestinal inflammation, termed colitis-associated colorectal cancer (CAC), represents a distinct clinical entity from sporadic colorectal cancer. Patients with long-standing inflammatory bowel disease face a markedly elevated risk of malignant transformation, and tumors in this setting are believed to emerge through repeated cycles of epithelial injury, repair, and exposure to a chronic inflammatory cytokine milieu rather than through the classical adenoma-carcinoma sequence driven by APC loss. This distinct pathogenesis has created demand for animal models that faithfully reproduce the inflammation-carcinoma axis, and the azoxymethane (AOM)/dextran sulfate sodium (DSS) model has become the benchmark for this purpose.

Fig 2: Reference figures for AOM/DSS-Induced Colorectal Cancer Model.Fig 1. Complete AOM/DSS protocol workflow (105–119 days): Step 1 carcinogenesis induction timeline (AOM 10 mg/kg i.p. on day 0, three 2.5% DSS 7-day cycles interleaved with normal water), Step 2 intraperitoneal injection of L012 chemiluminescent probe (30 min) for in vivo imaging, Step 3 Swiss-roll colon processing for histology, and Step 4 H&E staining and microscopy — an end-to-end SOP integrating tumor induction, in vivo chemiluminescence detection, and histopathology. (Sun, Wenbo, et al., 2023)

In this two-stage initiation-promotion system, AOM acts as a pro-carcinogen that is metabolically activated to a reactive methylating species, initiating DNA damage in colonic epithelial cells, while DSS administered in the drinking water disrupts the mucosal barrier and provokes recurring bouts of colitis that promote the outgrowth of initiated clones. Within 7 to 12 weeks, animals develop well-defined lesions that progress from aberrant crypt foci and adenomas to invasive adenocarcinomas, predominantly in the distal colon, a distribution that closely parallels human disease. Because the model is inexpensive, highly reproducible, compatible with virtually any genetic background, and suitable for both chemoprevention and therapeutic intervention studies conducted in vivo, it remains the workhorse of CAC research and preclinical drug evaluation.

Principles of AOM/DSS-Induced Colorectal Cancer Model Construction

The construction of the AOM/DSS model rests on a classical initiation-promotion principle: a genotoxic initiator fixes heritable mutations in colonic epithelial stem cells, and a non-genotoxic inflammatory promoter expands these initiated clones into macroscopic tumors. The key agents and their respective roles are summarized below.

Component / Stage Agent & Route Mechanism of Action Typical Parameters
Initiation Azoxymethane (AOM), single intraperitoneal injection A hepatic pro-carcinogen converted to methyloxonium ions that methylate DNA (notably O6-methylguanine) in colonic epithelium, causing mutations in oncogenes and tumor suppressors such as K-ras, β-catenin, and p53. 10–12.5 mg/kg body weight, one injection on day 0
Promotion Dextran sulfate sodium (DSS), drinking water A non-genotoxic, negatively charged polysaccharide (MW 36–50 kDa) that erodes the epithelial barrier and basolateral mucosa, triggering innate immune activation, neutrophil and macrophage infiltration, and chronic inflammation. 1.5–3% (w/v) in drinking water for 5–7 consecutive days per cycle
Inflammatory amplification Cytokine-rich microenvironment (TNF-α, IL-6, IL-1β, STAT3/NF-κB signaling) Repeated injury-repair cycles drive compensatory proliferation of initiated cells, reactive oxygen species production, and pro-tumorigenic signaling that accelerate clonal expansion and dysplasia. Peaks during and shortly after each DSS cycle
Tumor progression Spontaneous lesion evolution Initiated crypts progress through aberrant crypt foci, adenomas, and ultimately adenocarcinomas, mainly in the distal colon, mirroring the human colitis-associated sequence. Macroscopic tumors typically evident by week 10–12
Cycles & recovery Alternating DSS exposure and plain water Multiple DSS cycles (commonly three) with 14-day recovery intervals balance tumor induction efficiency against animal welfare, allowing epithelial regeneration between insults. 3 cycles of DSS, each followed by ~14 days of regular water

Our Services

Building on a decade of hands-on experience with chemically induced gastrointestinal tumor models, Alfa Cytology provides end-to-end AOM/DSS model construction tailored to each client's hypothesis, whether the goal is validating a chemopreventive agent, benchmarking an anti-inflammatory therapeutic, or interrogating tumor-immune interactions in vivo.

Workflow of AOM/DSS-Induced Colorectal Cancer Model Construction

A typical AOM/DSS study at Alfa Cytology proceeds over a 10- to 14-week window, integrating acclimatization, carcinogen priming, repeated colitis cycles, and comprehensive endpoint analysis. The essential steps are outlined below.

  1. Animal acclimatization and randomization: C57BL/6 or strain-of-choice mice aged 6–8 weeks are housed under specific pathogen-free conditions, habituated to bottled water, and randomized into treatment groups with age- and sex-matched controls.
  2. Baseline health assessment: Body weight, stool consistency, and overall condition are recorded before any manipulation to establish reference values for subsequent welfare monitoring.
  3. AOM administration (Day 0): A freshly prepared AOM solution is administered as a single intraperitoneal injection at 10–12.5 mg/kg body weight, calculated from precise individual weights.
  4. First DSS cycle (approximately Day 7): Drinking water is replaced with 1.5–3% DSS for 5–7 days, inducing acute epithelial injury; solution freshness is maintained by regular replacement.
  5. Recovery interval (approximately Days 14–21): DSS is withdrawn and plain water is provided for roughly two weeks, permitting mucosal regeneration while initiated clones expand.
  6. Repeated DSS cycles: The DSS-recovery sequence is repeated, most commonly for a total of three cycles, with dose titration applied as needed to balance tumor burden against animal welfare.
  7. Longitudinal monitoring: Animals are weighed and clinically scored daily during DSS exposure and several times weekly thereafter; weight loss thresholds, diarrhea, and occult or visible blood in stool guide supportive care and humane endpoints.
  8. Endpoint analysis: At the predefined endpoint (typically week 10–14), mice are euthanized; colons are excised, measured, and examined macroscopically for tumor number, size, and distribution, then processed for histopathology, immunohistochemistry, and molecular analyses.

Fig 3: Workflow for the establishment of AOM/DSS-Induced Colorectal Cancer Models.Fig 2. AOM/DSS-Induced Colorectal Cancer Model Construction Workflow.

Case Study-AOM/DSS-Induced Colorectal Cancer Model Development

Alfa Cytology has applied the AOM/DSS platform across a broad range of preclinical programs, supporting clients evaluating novel anti-inflammatory compounds, chemopreventive formulations, targeted inhibitors, and immuno-oncology strategies. In these studies, our team has delivered robust tumor induction with controlled inter-animal variability, coupled with comprehensive readouts spanning tumor burden quantification, histopathological grading of dysplasia and adenocarcinoma, inflammatory cytokine profiling, and biomarker analysis. Detailed case data and study-specific results can be shared upon request under appropriate confidentiality arrangements.

Fig 4: Case Study-AOM/DSS-Induced Colorectal Cancer Model Development.

Why Choose Alfa Cytology?

Clients select Alfa Cytology for AOM/DSS model work because the service combines scientific depth with operational reliability, translating into data that stands up to scrutiny.

  • Customized study design aligned with each client's mechanism of action, dosing schedule, and endpoint requirements.
  • Optimized, strain-specific AOM and DSS dosing refined through internal titration to maximize tumor incidence while safeguarding animal welfare.
  • Rigorous longitudinal monitoring with predefined humane endpoints and daily welfare scoring during colitis cycles.
  • Integrated endpoint package covering macroscopic tumor mapping, histopathology, immunohistochemistry, and molecular profiling under one workflow.
  • High reproducibility achieved through standardized husbandry, microbiota-aware practices, and strict protocol harmonization across cohorts.
  • Dedicated Ph.D.-level scientific support from study design through data interpretation and report delivery.

Contact Us

Ready to advance your colorectal cancer research program with a rigorously controlled AOM/DSS model? Alfa Cytology welcomes the opportunity to discuss your project objectives, timeline, and endpoint needs. Contact us today or reach out to our scientific team to receive a customized proposal and quotation tailored to your preclinical study.

Reference

  1. Sun, Wenbo, et al. "Protocol for colitis-associated colorectal cancer murine model induced by AOM and DSS." STAR protocols 4.1 (2023).

For research use only. Not intended for any clinical use.

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