# PORPHYRIN PHOTOSENSITIVITY OF SKIN:  MECHANISTIC STUDIES

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1987 · $117,365

## Abstract

Porphyrin photosensitization of the skin is a major health problem for
patients suffering from certain types of human porphyria and for
individuals treated with hematoporphyrin derivative (HPD) and light
(photoradiation therapy) for cancer.  Porphyrins are resonating structures
(tetrapyrroles) which can absorb radiant energy in the visible spectrum
(400-700 nm) and when present in increased amounts in living cells can
cause phototoxic damage.  It is generally believed that porphyrin
photosensitization is a photodynamic process which occurs as a consequence
of the generation of reactive species of oxygen; however, little is known
regarding the role of these agents in porphyrin photosensitization of the
skin.  The subcellular sites of cutaneous phototoxic injury evoked by
porphyrins have also not been rigorously defined.  The hypothesis to be
tested in this proposal is that lipid-rich membranous structures of the
cell such as plasma membranes, mitochondria, lysosomes and endoplasmic
reticulum are potential targets for the injurious response evoked by
porphyrin photosensitization in the skin; that one or another species of
active oxygen mediates this response; and that peroxidation of lipid-rich
subcellular membranes is the fundamental mechanism of phototoxic injury.
It is planned to conduct a systematic series of studies in cultured Balb/C
mouse keratinocytes and fibroblasts and in the dermis and epidermis of the
same strain of animals in an effort to assess the relative phototoxic
effect of porphyrin photosensitization on these subcellular fractions.
Enriched preparations of plasma membranes, lysosomes and mitochondria will
be obtained using a metrizamide gradient technique and endoplasmic
reticulum will be prepared by differential centrifugation.  Marker enzymes
will be assayed to verify the fractionation procedure and to determine the
effects of porphyrin photosensitization on particular subcellular
membranes.  Lipid peroxide malondialdehyde will be measured as a marker for
membrane lipid peroxidation.  The long range goal of these studies is to
determine whether cutaneous phototoxicity evoked by porphyrins of different
solubility characteristics produces damage to specific subcellular
organelles and to define the species of reactive oxygen that mediate(s)
this cutaneous inflammatory response.  Knowledge obtained in these studies
may lead to the development of new strategies to reduce or eliminate
porphyrin photosensitization, resulting in more effective therapeutic
approaches to the management of cutaneous porphyria and to an improved
therapeutic index for photoradiation therapy of human cancer.

## Key facts

- **NIH application ID:** 3156813
- **Project number:** 5R01AR034368-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** DAVID RINSEY BICKERS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $117,365
- **Award type:** 5
- **Project period:** 1985-09-20 → 1988-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156813

## Citation

> US National Institutes of Health, RePORTER application 3156813, PORPHYRIN PHOTOSENSITIVITY OF SKIN:  MECHANISTIC STUDIES (5R01AR034368-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156813. Licensed CC0.

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