Environmental and Molecular Mutagenesis - Legacy Tobacco ...

200 1989 EMS Abstracts
Notes . ,,that.ERCC2 is requiiedAsreeU viability as well as repair, as in the case of RAD3 . The gross underrepresentation
of CHO mutants recovered in the ERCCZ complementation group upon treatment with the
frame shift agent ICR170rther suggests an essential function. Two other human genes, XRCCJ (X-ray
Repair Cross Compl XRCC2, which help repair Ionizing radiation damage, were assigned to
chromosomes 19 and 7, respectively . Analysis of cosmid clones of XRCCJ shows that this gene, which is
33 kb in length efficiently corrects CHO mutant EM9 . The phenotype of EM9 is defective rejoinin~ of
strand breaks and greatly elevated sister chromatid exchange (SCE) . The cDNA clone pXRI-30, obtauted
from the pcD2 library, gave stable but incomplete correction of EM9 . Nucleodde sequencing showed that
this clone lacked 26 nucleotides of protein coding region. The XRCCI protein, which appears to be 633
a.a. in length, remains to be identified in terms of itsbiochemicai function in repair and SCE . This work
was done under the auspices of the U.S . Dept. of Energy by 1.LN1, under contract No . W-7405-ENO-48 .
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
580
MOLECULAR APPROACHES TO CARCINOGENESIS : ONCOGENE INDUCED TRANSFORMATION AND LINEAGE
SWITCHING OF RAT LIVER EPITHELIAL CELLS . Snorri S . Thorgeirsson, Laboratory of
Experimental Carcinogenesis, Division of Cancer Etiology, National Cancer Institute,
National Institutes of Health, Bethesda, MD 20892
Tumors produced by a chemically transformed rat liver epithelial (RLE) cell line
and its single cell-derived clonal subpopulations demonstrate wide-ranging morphological
presentations including carcinomas, sarcomas, "mixed epithelial-mesenchymal"
tumors, and undifferentiated tumors (Am . J . Pathol . 127 : 168-181, 1987) . To address
the question of heterogeneity of tumors er ve rom transformed RLE cells, we have
used recombinant retroviruses containing the following transforming oncogenes :
v-raf (3611-MSV), v-raf/v-myc (J2), v- c(J5), and v-Ha-ras (pRNR16) . A11 of the
oncogenes, with the exception of v-styc~J5), were efficient transforming agents in
the RLE cells . Tumors derived from the v-raf- and, to a lesser extent, those from
v-Ha-ras-transformed RLE cells showed mixed epithelial-mesenchymal morphology,
whereas the combination of v-raf/v-myc (J2) consistently produced differentiated
trabecular carcinomas . These data suggest that the lineage commitment of the RLE
cells can be perturbed by a single transforming oncogene and that different tumor
types derived from these cells may reflect the expression of a selective oncogene
or a combination of oncogenes .
581
METABOLISM OF1-NITROPYRENE TO A MUTAGEN IN CAO CELLS BY NITROREDUCTION . Janice R .
Thornton-Manning, Beverly A . Smith, Roberta A . Mittelstaedt, Frederick A . Beland and
Robert H . Heflich, University of Utah, Salt Lake City, UT (USA), and National Center
for Toxicological Research, Jefferson, AR (USA)
Nitroreduction of 1-nitropyrene (1-NP), a tumorigenic environmental contaminant, to
N-hydroxy-l-aminopyrene (N-hydroxy-l-AP) is an important pathway for DNA adduct formation
in vivo . In previous studies, treating Chinese hamster ovary (CHO) cells with
1-NP for up to 5 hr produced low levels of a DNA adduct indicative of nitroraduction,
but no mutants were induced . In this study, CHO-KI-SH4 cells and repair-deficient CHO
UV5 cells were incubated with 40 uM 1-NP for up to 24 hr . While none of the CHO-R1
treatments induced mutants, treatment of UV5 cslls for 12 and 24 hr induced 5 and 12
mutants/106 clonable cells (different from control at p