Chromosome Damage and Dna Repair Induced in Human Fibroblasts by Uv and Cholesterol Oxide

Abstract

Sumniar>\ In luiniaii lilirolblasts. cholesU-rol oxide induced a similar degree of chrnnuwome damage (H-(i% of inetaplia.st's) and DNA repair synthesis (8-10^ of cells with lijjlitl>-lai)i'llL'd nuclei) iw low dtwes of ultraviolet litilit (UV), but did not produLc single-stratid DN.A breaks or UiN.A diuinijic detectable hy inhibition of th\inidiiie incnrpuratiini. f^hroniosoiiie aberrations were deteeted up to S week.s iifter treatment with cholesterol oxide and VW C<nni>ined treatments had almost additixe ellect.s ini the frequency iif chrotnosonie aberrations liut mit im repair s\ntht'sis. Multiple daily doses of UV did not came more atx'rrations than a single dose, Attempts to transfiirn] two fibroblast strains from nfirinal donors and three derived from nielaiiotna patients using siiiHlc atid combined treatments of U\', cholesterol oxide and hypertherniia ( !()°) were unsiicce.ssful. IXTRODICTION.The strong circumstantial evidence for a role tjf solar-derived UV in the aetiolog\-of huniati .skin cancer (Urhacli, 1975) aticl the ability of UV to trans-(ortn cultured rodent cells (CMian and Little. 1976;DiPaolo and Donovan. 1976; Mntidal atld Ili'idelherger, 1976) enconrages attetnpts to tran.storin normal human cells by UV in vitro. Au expcrinietital model of this type wt)uld be vahtabK' for testing hypotheses coticerning the iiidttction and prevention of skin Itiiiiottrs in man. Thai snili a s\stein ha.s tiot yi't l)een reported ina\' be due to the more efficient DNA excision repair systetu it) human cells or a requirement for promoting factors sueh as chemical.s, viruses or other solar \va\elengths (Frectiiiui atid Kiit) x, 1965;Goss and Parsons. 1976; Mondal and Heidelln-rger, 1976). Alternatively, if UV should act indirectly through the in situ Formation of a chemical carcinogen, then tratisformation tnight best be eflFected b\' direct administration of the coinponnd. Gholesterol-a-oxide, for example, would appear

Physiologic, biochemical, and cytologic aspects of nipple aspirate fluid

“…Higher levels of cholesterol are associated with the presence of cholesterol 5a,6c~-epoxide and cholesterol 5f3,6[3-epoxide and their corresponding triol. These substances have been reported to induce sarcomas (38), transform embryo hamster and human lung cancer cell lines in vitro (39,40), and induce DNA damage in vitro (41). Sevanian and Peterson (40) have reported that cholesterol epoxides are direct-acting mutagens.…”

Wide‐Bore Capillary Gas Chromatographic Method for Quantification of Cholesterol Oxidation Products in Egg Yolk Powder

“…Considerable attention has recently been devoted to cholesterol oxidation products as a result of toxicological studies attributing adverse biological activities to many of these compounds. Cholesterol-5or,6or-epoxide (wCE) has been associated with atherogenesis (Gray et al, 1971;Imai et al, 1976), carcinogenesis (Bischoff, 1969;Black and Lo, 1971;Black and Chan, 1976) and various other toxic effects (Blackburn et al, 1979;Kandutsch and Chen, 1978;Parsons and Goss, 1978). 7cx-Hydroxycholesterol, 7P-hydroxycholesterol and 7-ketocholesterol have also been shown to exhibit toxicological properties (Kandutsch and Che!, 1973).…”

Effects of Thymidine Analogues on Murine and Human Cells

“…Tbe origins oftbe human melanoma cell lines and fibroblasts and tests for .Mycoplasma have been described (Parsons c/j/.. 1974;Parsons and Goss, 1978). Tbeclonesof mouse melanoma (B-16), Lewis lung tumour (LLT) and methy!cholanthrene-inducedfibrosarcomas(MC-2 and JR-2) were kindly provided by Dr. J. W. Sheridan.…”