From benign, brown age spots to malignant melanoma, the skin'smelanocytes have a lot to answer for.

These cells manufacture the pigment melanin, which imparts shadesof light and dark color not only to the skin but to the eye's iris andthe hair's hue _ to name only the main melanin-tinted parts of thebody.

As the body grows older, over-deposition of melanin splotches hands,arms and face (to mention only the all-too-visible cutaneous sites)with senile melanoderma. At the same time, a gene involved insynthesizing melanosomes _ the melanin pigment particles _ andaptly named the silver gene, progressively grays the hair of agingmice and humans. It does so, presumably, by causing premature deathof hair-follicle melanocytes.

These cosmetic stigmata fuel much of the cosmetics industry. Todate, its ministrations have been less than skin-deep, for lack ofinsight into the complex interplay of genes and their proteins, whichdrive the melanotic pathway.

Meanwhile, for most of the 1990s, biochemist/molecular biologistVincent Hearing, and his colleagues at the National Cancer Institute(NCI), together with dermatologists in Japan, have been teasing outthe cell biology of mammalian melanocytes.

Hearing tells BioWorld Today that NCI is now seeking to enlist "apharmaceutical or cosmetic company that can effectively pursue thescientific and commercial generation and development of agentsinhibiting pigmentation."

The March 21 Federal Register published this announcement:"Opportunity for a Cooperative Research And DevelopmentAgreement (CRADA) for the scientific and commercial developmentof diagnostic and/or therapeutic agents for hyperpigmentary lesions."

Hearing, a research scientist in the NCI's Laboratory of Cell Biology,said: "The purpose of this CRADA is to examine the question ofwhat mechanisms inhibit hyperpigmentation, and then come up withpotential ways of down-regulating melanin production in a particulararea to make it mimic the normal surrounding pigmentation."

He and his co-workers have identified, cloned and characterized fourof the genes that cause melanocytes to differentiate, proliferate andsurvive, seven that control that cell's functioning, and fourresponsible for melanosome (pigment) function.

These genes bear such descriptive names as splotch, pallid, pearl,pink-eyed and silver. Hearing described to a recent melaninsymposium "the incredibly complex series of controls that areoperating to regulate the nature of melanins produced within abiological system, especially within mammalian melanocytes."

"We have antibodies as well as nucleotide probes to a number of themelanogenic proteins," he told BioWorld, "of which several arerelated to tyrosinase, a key enzyme in melanocyte function." Headded, "We would tell the successful CRADA applicant: `Takewhatever putative agents you might be able to design, and test themfor efficacy in inhibiting pigmentation in localized areas.'"

Besides such an agent's obvious cosmetic interest, Hearing pointedout, "it does have potential application to melanoma, or any type ofskin cancer, for that matter, in that it will address the mechanismsinvolved in controlling pigmentation, which is directly related to skincancer, including melanoma."

He cited "such clinically abnormal hyperpigmentation occurs inpostinflammatory conditions, wound-healing, sun-damaged skin andother pigmentary disorders."

Editor's Note: For information concerning this CRADA opportunity,consult Bert Zbar or Mark Noel, NCI Office of TechnologyDevelopment, (301) 496-0477. For science-related questions, theymay arrange consultation with Vincent Hearing at the Laboratory ofCell Biology. n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.