Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Cancer chemotherapy often causes temporary baldness. What happens is that the DNA-damaging drugs that attack the fast-dividing cells of malignant tumors also go after the fast-dividing healthy cells of hair follicles. That alopecia then prompts the cells to self-destruct by the natural process of apoptosis - programmed cell death. Why then, the question arises, don't those drugs lay waste to all the healthy calls in the cancer patient's body? The answer is that it's not known why chemotherapeutic compounds don't elicit apoptosis in healthy cells. The standard alibi is that tumor cells are dividing, normal cells are not.

"But that's an observation, not an explanation," said surgeon Steve Weinraub, at Washington University in St. Louis. He is senior author of a paper in the Oct. 4, 2002, issue of the journal Cell. Its title: "Bcl-xL deamidation is a critical switch in the regulation of the response to DNA damage." (Deamidation is a process that removes the NH₂ group from an amino compound.)

"Our findings show that if Bcl-xL is inactivated by deamidation," Weinraub stated, "DNA-damaging chemotherapy will kill even healthy cells." The Cell paper explains that noncancerous, nondividing cells have a biochemical switch that triggers apoptosis when turned on. Bcl-xL is the protein that houses that switch. The study focuses on the family of Bcl-2 proteins, which play a central role in both promoting and inhibiting apoptosis.

The co-authors first exposed malignant cells from bone, ovarian and other tumors to the anticancer drug cisplatin. When they examined the Bcl-2 proteins from the cells that had died by apoptosis, they found that, in each case, Bcl-xL had been modified by deamidation, which makes slight changes in two amino acids in Bcl-xL. Those changes altered the shape of the protein and inactivated it. It then released the second amino acid, allowing programmed cell death to proceed.

The team also exposed a line of healthy, nondividing human fibroblasts and several lines of mouse fibroblasts to cisplatin. In some of those cells, they had artificially inactivated Bcl-xL. They found that cells harboring normal Bcl-xL were not affected by the drug, while those with the inactive compound died by apoptosis, indicating they were now susceptible to cisplatin.

"Our findings," Weinraub said, "show that normal cells somehow suppress the signal that throws the switch and avoid self-destructing. They also suggest," he concluded, "that tumor cells that suppress the same signal might be resistant to chemotherapy drugs."

Mouse Experiments Define Sexual Differences Between Male, Female Chromosomes, Brains

Years ago, the then-politically incorrect French Parliament debated whether women in the work force should get equal pay with men. One delegate stood up to remind the lawgivers, "After all there is a certain difference between men and women." To which the chamber resounded with cries of "Vive la differénce!"

This often-remembered glass-ceiling anecdote here moves from politics to neurology. A paper in Nature Neuroscience, released online Sept. 16, 2002, bears the title: "Sex chromosome genes directly affect brain sexual differentiation." Its authors are neuroendocrinologists at the University of California at Los Angeles.

"Sex differences in the brain," the paper leads off, "are caused by differences in gonadal secretions: Higher levels of testosterone during fetal and neonatal life cause the male brain to develop differently than the female brain. In contrast," it continues, "genes encoded on the sex chromosomes are not thought to contribute directly to sex differences in brain development, even though male (XY) cells express Y-chromosome genes that are not present in female (XX) cells, and XX cells may have a higher dose of some X-chromosome genes."

Using mice in which the genetic sex of the brain (XX vs. XY) was independent of gonadal phenotype (testes vs. ovaries), the co-authors found that XY and XX brain cells differed in phenotype, indicating that a brain cell's complement of sex chromosomes may contribute to its sexual differentiation.

Results of their mouse experiments "draw further attention to mesencephalic dopamine systems as potential sites of direct X or Y gene action during sexual differentiation of the brain, and raise the question of the site and mechanism of action of the sex chromosomes in neuronal development in vivo." The UCLA paper's finding "offers significant advantages for unraveling the cellular and molecular mechanisms of sex-chromosome gene action" in rodents and humans.

TZD, New Oral Antidiabetic Remedy, Makes Fat Make Fat, Which Makes For Weight Gain

TZD stands for "thiazolidinedione."

Thiazolidinedione stands for a promising new class of antidiabetic drugs. It's being prescribed for oral management of Type II diabetes mellitus, also known as adult-onset or non-insulin-dependent diabetes. TZD apparently lowers insulin resistance, which is the hallmark of Type II diabetes.

However, the drug comes with hang-ups, among them side effects such as excess weight gain. This is ironic as TZD is usually prescribed to be taken together with diet and exercise. Its precise mechanism of action has remained largely unknown. New research is now shedding light on both TZD's heavy side effect and its mysterious mode of action.

Nature Medicine carries an article published online Sept. 23, 2002, titled: "A futile metabolic cycle activated in adipocytes by antidiabetic agents."

The key seems to be fat cells - adipocytes. The paper's co-authors, at the University of Pennsylvania in Philadelphia, report that TZDs encourage these cells to take up the building blocks of fat - namely, fatty acids - from the bloodstream. These are then converted to triglycerides, the whitish substance known pure and simple as fat. Thus, TZDs make fat cells make fat - hence the side effect. But it's also known that fatty acids in the bloodstream cause a blunted sensitivity to insulin in diabetics. So by sucking fatty acids out of the bloodstream, TZDs may be making the body more sensitive - less resistant - to insulin.