Quantitative trait locus mapping of susceptibilities to butylated hydroxytoluene-induced lung tumor promotion and pulmonary inflammation in CXB mice

被引:31
作者
Malkinson, AM
Radcliffe, RA
Bauer, AK
机构
[1] Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO 80262 USA
[2] Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA
关键词
D O I
10.1093/carcin/23.3.411
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We have reported previously [BauerA.K. et al. (2001) Exp. Lung Res., 27, 197-216] that the 13 CXB recombinant inbred mouse strains derived from BALB/cByJ and C57BL/6J progenitors vary in their responsiveness to both lung tumor promotion and pulmonary inflammation induced by chronic administration of butylated hydroxytoluene (BHT). Herein we have applied these data, along with markers known to be polymorphic among these strains, to conduct linkage analysis of these susceptibilities. This enabled us to assign provisional quantitative trait loci (QTL) that govern these strain variations in susceptibility as a genetic approach to assessing the influence of inflammation on tumorigenesis. A Chr 15 (39.1-55.6 cM) QTL regulated susceptibility to two-stage carcinogensis, a protocol in which chronic BHT exposure followed a single urethane injection; a similar QTL on Chr 15 (46.7-61.7 cM) influenced BHT induction of cyclo-oxygenase-2 (COX-2) expression. A Chr 18 (37-41 cM) QTL modulated both the number of lung tumors induced by 3-methylcholanthrene (MCA) injection with subsequent treatment with BHT as well as BHT-induced ingress of macrophages into airways. Other chromosomal sites that affected either the degree of BHT-elicited macrophage infiltration, Chr 9 (48-61 cM), or COX-2 induction, Chr 10 (59-65 cM), were reported to influence susceptibility to lung tumorigenesis in other strains. The fact that common chromosomal locations regulate both inflammation and carcinogenesis suggests a pathogenic role of inflammatory mediators in tumor development that may be exploited for chemoprevention of lung cancer.
引用
收藏
页码:411 / 417
页数:7
相关论文
共 54 条
[1]   FETAL MOUSE SUSCEPTIBILITY TO TRANS-PLACENTAL LUNG AND LIVER CARCINOGENESIS BY 3-METHYLCHOLANTHRENE - POSITIVE CORRELATION WITH RESPONSIVENESS TO INDUCERS OF AROMATIC HYDROCARBON METABOLISM [J].
ANDERSON, LM ;
JONES, AB ;
RIGGS, CW ;
OHSHIMA, M .
CARCINOGENESIS, 1985, 6 (09) :1389-1393
[2]  
[Anonymous], 1986, FUNDAMENTALS ONCOLOG
[3]   Cancer resistance genes in mice: models for the study of tumour modifiers [J].
Balmain, A ;
Nagase, H .
TRENDS IN GENETICS, 1998, 14 (04) :139-144
[4]   Butylated hydroxytoluene (BHT) induction of pulmonary inflammation: A role in tumor promotion [J].
Bauer, AK ;
Dwyer-Nield, LD ;
Keil, K ;
Koski, K ;
Malkinson, AM .
EXPERIMENTAL LUNG RESEARCH, 2001, 27 (03) :197-216
[5]   The lung tumor promoter, butylated hydroxytoluene (BHT), causes chronic inflammation in promotion-sensitive BALB/cByJ mice but not in promotion-resistant CXB4 mice [J].
Bauer, AK ;
Dwyer-Nield, LD ;
Hankin, JA ;
Murphy, RC ;
Malkinson, AM .
TOXICOLOGY, 2001, 169 (01) :1-15
[6]   High cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) contents in mouse lung tumors [J].
Bauer, AK ;
Dwyer-Nield, LD ;
Malkinson, AM .
CARCINOGENESIS, 2000, 21 (04) :543-550
[7]  
BENFIELD JR, 1998, BIOL LUNG CANC, P247
[8]  
COHEN BH, 1977, LANCET, V2, P523
[9]   Secretory phospholipase Pla2g2a confers resistance to intestinal tumorigenesis [J].
Cormier, RT ;
Hong, KH ;
Halberg, RB ;
Hawkins, TL ;
Richardson, P ;
Mulherkar, R ;
Dove, WF ;
Lander, ES .
NATURE GENETICS, 1997, 17 (01) :88-91
[10]   Quantitative trait locus mapping of airway responsiveness to chromosomes 6 and 7 in inbred mice [J].
De Sanctis, GT ;
Singer, JB ;
Jiao, A ;
Yandava, CN ;
Lee, YH ;
Haynes, TC ;
Lander, ES ;
Beier, DR ;
Drazen, JM .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1999, 277 (06) :L1118-L1123