Fibroblast cell lines from young adult mice of long-lived mutant strains are resistant to multiple forms of stress.
Previous studies have shown that dermal fibroblast cell lines derived from young adult mice of the long-lived Snell dwarf mutant stock are resistant, in vitro, to the cytotoxic effects of H(2)O(2), cadmium, UV light, paraquat, and heat. We show here that similar resistance profiles are seen in fibroblast cells derived from a related mutant, the Ames dwarf mouse, and that cells from growth hormone receptor-null mice are resistant to H(2)O(2), paraquat, and UV but not to cadmium. Resistance to UV light, cadmium, and H(2)O(2) are similar in cells derived from 1-wk-old Snell dwarf or normal mice, and thus the resistance of cell lines derived from young adult donors reflects developmental processes, presumably hormone dependent, that take place in the first few months of life. The resistance of cells from Snell dwarf mice to these stresses does not reflect merely antioxidant defenses: dwarf-derived cells are also resistant to the DNA-alkylating agent methyl methanesulfonate. Furthermore, inhibitor studies show that fibroblast resistance to UV light is unaffected by the antioxidants ascorbic acid and N-acetyl-L-cysteine. These data suggest that postnatal exposure to altered levels of pituitary hormones leads to development of cellular resistance to oxidative and nonoxidative stressors, which are stable through many rounds of in vitro cell division and could contribute to the remarkable disease resistance of long-lived mutant mice.
Salmon
Adam B
AB
Cellular and Molecular Biology Graduate Program, University. of Michigan School of Medicine, 1500 E. Medical Center Dr., 5316 CCGC 0940, Ann Arbor, MI 48105-0940, USA.
Murakami
Shin
S
Bartke
Andrzej
A
Kopchick
John
J
Yasumura
Kyoko
K
Miller
Richard A
RA
D000375:Aging / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002460:Cell Line; D004351:Drug Resistance; D004392:Dwarfism / Q000235:genetics / Q000503:physiopathology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008136:Longevity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects*; D010907:Pituitary Hormones / Q000172:deficiency / Q000235:genetics; D011836:Radiation Tolerance; D014466:Ultraviolet Rays
D000975:Antioxidants; D010907:Pituitary Hormones; D002104:Cadmium; D006861:Hydrogen Peroxide