# RADIATION AND DRUG EFFECTS IN MAMMALIAN CELLS

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 1993 · $150,000

## Abstract

Our long term goal is to understand how radiation and drugs interact in
cells.  To study this, a series of multidrug resistant Chinese hamster
cell lines were produced by selection in increasing levels of ADRM,
culminating in LZ-100 (grown in 100 mu-g/ml).  LZ-100 cells exhibit three
mechanisms of resistance: enhanced drug efflux via P-glycoprotein (P-gp),
increased inactivation of ADRM cytoxicity by structural modification of
the molecule, and sequestration of ADRM into vesicles.  The hypothesis to
be tested is that radiation exposure produces cell membrane effects that
impair the sequestration of ADRM into vesicles by LZ-100 after ADRM
treatment.  The specific .aims are to: 1) characterize the drug
sequestration mechanism in LZ-100; 2) determine the effect of radiation
on the drug sequestration mechanism; and 3) determine the relative
importance of radiation induced membrane damage in affecting vesicle
formation.  Aim 1 will be accomplished by utilizing electron microscopy
to determine the origin of vesicles, determining the presence of P-gp in
isolated vesicles using antibody staining and Western blotting, blocking
P-gp externally on LZ cell membrane to determine if vesicle formation is
inhibited and identifying vesicle contents using HPLC and searching for
lysosomal enzymes.  Aim 2 will be accomplished by quantitating the effect
of radiation on vesicle formation using light and electron microscopy,
quantitating cell survival after radiation/ADRM treatment, and
quantitating membrane turnover.  Aim 3 will be accomplished by comparing
the ability of membrane damaging agents with DNA damaging agents to
inhibit vesicle formation in LZ-100.  If X-irradiation does effect the
drug sequestration mechanism in LZ-100, this suggests that the cell
membrane is important in the cellular response to radiation.  In
addition, these studies will provide important information concerning how
the drug sequestration mechanism functions and its significance to
multidrug resistance, the function of P-gp in vesicle formation/function,
the effect of radiation on the drug sequestration mechanism, and will
allow new, combined (drug and radiation) therapeutic strategies for human
cancer to be formulated.

## Key facts

- **NIH application ID:** 3171993
- **Project number:** 2R01CA034269-09A1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **SAM.gov UEI:** MSPWVMXXMN76
- **Principal Investigator:** JAMES A BELLI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $150,000
- **Award type:** 2
- **Project period:** 1982-07-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171993

## Citation

> US National Institutes of Health, RePORTER application 3171993, RADIATION AND DRUG EFFECTS IN MAMMALIAN CELLS (2R01CA034269-09A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171993. Licensed CC0.

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