# Project 4: Using Adductomic Signatures to Evaluate Risks of Superfund Chemicals

> **NIH NIH P42** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $292,053

## Abstract

PROJECT 4: SUMMARY/ABSTRACT
Although reactive electrophiles are important contributors to states of human health and disease, these
molecules are generally overlooked in exposomic investigations. For example, many electrophiles are
inherently toxic and carcinogenic because they modify human DNA and proteins, but are too reactive to be
measured in blood. One approach for investigating exposures to reactive electrophiles involves measurement
of adducts formed from reactions with blood proteins. Human serum albumin (HSA) contains a nucleophilic
hotspot (Cys34), which is the major scavenger of reactive oxygen species and other electrophiles that enter
the blood from inhalation, ingestion and metabolism. Our laboratory has developed an untargeted assay
(`adductomics') for profiling HSA-Cys34 adducts and has compiled a library of over a hundred such adducts
detected in human blood. Interestingly, some adducts are specific to particular exposures (e.g., benzene oxide
from benzene) while others relate more generally to oxidative stress and dysregulation of metabolic pathways
(e.g. Cys34 oxidation products and disulfides of circulating thiols). We hypothesize that this combination of
chemical-specific and oxidative-stress adducts in blood establishes patterns or `signatures' of adducts that can
be related to subjects' exposures to Superfund contaminants and their interactions with environmental
stressors. By profiling HSA adducts in blood from cross sectional studies of populations heavily exposed to
three Superfund chemicals (benzene, PAHs & arsenic), we propose to find their adductomic signatures. Then,
by targeting these adductomic signatures in archived serum from a large cohort study being conducted by the
National Cancer Institute in Shanghai, China, we will investigate contributions of benzene exposure on risks of
lymphoid and myeloid cancers and of PAH and arsenic exposures on risks of lung cancer.
 Project 4 will directly address Problems 3 & 4 on mixtures/complexity by examining a plethora of
adducts associated with exposures to Superfund chemicals and environmental stressors. Since Project 4 will
explore the use of adductomic signatures as biomarkers of past exposure in prospective studies of cancers, it
also directly addresses Problem 2. Project 4 will provide insights to Project 3 regarding protein modifications
and bioactivation pathways, to Project 1 regarding mechanisms by which arsenic causes cancer in humans,
either alone or in conjunction with psycho-social stress and obesity, and to Projects 2 and 5 regarding
contributions of reactive intermediates to toxicity and degradation.

## Key facts

- **NIH application ID:** 10136017
- **Project number:** 5P42ES004705-33
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Stephen Morris Rappaport
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $292,053
- **Award type:** 5
- **Project period:** 1997-04-01 → 2022-08-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136017

## Citation

> US National Institutes of Health, RePORTER application 10136017, Project 4: Using Adductomic Signatures to Evaluate Risks of Superfund Chemicals (5P42ES004705-33). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10136017. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*