By David N. Leff
Editor's note: Science Scan is a roundup of recently published, biotechnology-relevant research.
Remember the Marlboro Man? That grizzled cowboy with the crow's-foot wrinkles around his eyes symbolized for years the wise, venerable, paradigmatic poster boy with the cigarette between his lips.
Now a research study suggests that those facial wrinkles came not just from age but from smoking itself. Dermatologists at King's College, London, initially were probing the effects of solar ultraviolet (UV) radiation on skin. They measured the induction of matrix metalloproteinase on the bare buttocks of 33 young-adult volunteers - 21 men, 12 women - exposed to sun-lamp UV treatment.
Matrix metalloproteinase (MMP) degrades dermal collagen, the major protein of connective tissue in mammals, including man. It accounts for at least 70 percent of the dry weight of dermis. Collagen is important in maintaining the mechanical/elastic properties of skin.
The researchers noticed that in their in vivo experiment, some volunteers had little or no MMP messenger RNA in their buttocks before UV exposure, whereas in other subjects the protease was readily detectable. The team retrospectively asked the volunteers about their smoking status, and compared MMP concentrations with a tissue inhibitor of the metalloproteinase in smokers - (three women, 11 men) and non-smokers - (nine women, 10 men). Most smokers reported having used 10 to 20 cigarettes a day for three to 25 years.
Full-thickness, 4-millimeter skin biopsies and polymerase chain reaction confirmed that smoking induces MMP mRNA in skin in vivo, but had no effect on the tissue inhibitor. Their report, in the March 24, 2001, issue of The Lancet, bears the cryptic title: "Matrix metalloproteinase-1 and skin aging in smokers." It made the point, "Smokers look older than non-smokers of the same age," and concluded, ". . . the multiplicative effects of sunlight and smoking on facial aging occur by induction of MMP-1."
Are Staph aureus Bacteria That Calmly Colonize People's Nostrils Same Type As Infectious Killers?
Staphylococcus aureus is one of the most important bacterial pathogens of humans. A major scourge of hospital infections, particularly causing serious endovascular, wound, bone and joint infections, while evading the immune system, makes it a major public health burden. Compounding this scourge is the increased prevalence of antibiotic-resistant strains.
But S. aureus has a benign Jekyll-like, as well as a malign Hyde-like, nature. It also makes a peaceful commensal living, without symptoms, in the nostrils of a large proportion of the human population. This two-faced bacterial habitus raises the questions: Are all S. aureus equally virulent, and infection purely opportunistic, or is invasive disease mainly caused by a subset of particularly virulent genotypes untypical of the general population? How do the genetically and biochemically complex factors that promote virulence contribute to the evolutionary success of these commensal bacteria?
Tropical medicine epidemiologists at the University of Oxford, England, compared genetic typing of bacteria harvested from the nostrils of asymptomatic people with strains infecting hospital patients. Their findings suggested that whatever makes the bugs better nasal colonizers also makes these same strains smarter at causing disease.
Their report, in the April 6, 2001, issue of Science, is titled: "A link between virulence and ecological abundance in natural populations of Staphylococcus aureus." It concludes that results show hypervirulent clones of S. aureus to be abundant among the nostril-squatters, and that it is not solely an opportunistic pathogen.
Cancer-Causing Chemicals Lurking In Common Foods Cripple DNA Repair, Chromosome Stability
Several compounds commonly found in food are carcinogens, but their cancer-causing mechanism has been a black box. Now researchers at the Johns Hopkins Oncology Center have linked these oncogenic factors to genetic events that promote malignancy. They further show that each such event results in a different form of DNA instability. One leads to errors in DNA replication, the other to abnormal chromosomes.
The two carcinogens carry the license plates PhiP and MNNG. PhiP is abundant in Western diets, as found in well-done beef and chicken. It has also been shown to cause a variety of cancers in experimental animals.
MNNG, produced in the colon during food metabolism, proved potently carcinogenic in rats.
In the human digestive tract, cells are exposed nonstop to carcinogens such as PhiP and MNNG, with factors the likes of diet and genetic makeup determining their concentration. In their in vitro experiments, the researchers treated immortal, genetically stable human cells with the two food-related carcinogens. Most of the cells died after this treatment, but those that survived MNNP all had mutations in one mismatched repair gene. It led to an inability to efficiently mend errors of DNA replication. Accumulations of these mistakes are a recipe for tumor development, the researchers point out.
After PhiP exposure, human cells left alive showed abnormal chromosome numbers, which can also bring on cancer.
The Johns Hopkins research is reported in the April 10, 2001, issue of the Proceedings of the National Academy of Sciences, under the title: "Carcinogen-specific induction of genetic instability."
Lessons In Mechanisms Of Lung Carcinogenicity Proffered By A Breed Of Sheep (Not Cloned)
Jaagsiekte sheep harbor a retrovirus that causes a contagious lung cancer in those animals. A highly similar human malignancy causes 25 percent of all pulmonary carcinomas in the U.S. The sheep cancer, ovine pulmonary carcinoma, closely resembles human bronchioalveolar carcinoma, which is not related to smoking. Its origin is a mystery.
Some cancer-causing viruses have special genes that induce malignant transformation in cells; others activate oncogenes in the animals they infect.
Two articles in the Proceedings of the National Academy of Sciences, dated April 10, 2001, report research on the Jaagsiekte sheep retrovirus. Their authors are at the Fred Hutchinson Cancer Research Center in Seattle and the University of California, at Irvine. n