Genetic alteration of chromosome 8 is a common feature of human mammary epithelial cell lines transformed in vitro with benzo[a]pyrene

While some epidemiological risk factors for breast cancer have been identif ied, the environmental factors responsible for transformation of mammary ep ithelial cells are not clear. We have exposed the spontaneously immortalize d human mammary epithelial cell line MCF-10A to benzo[a]pyrene and selected transformed clones based on a loss of contact inhibition and anchorage-dep endent growth. Cytogenetic studies showed that each of the transformed subl ines possess an isochromosome 8q aberration. The c-Myc proto-oncogene, whic h is positioned at 8q24, was analyzed fur changes in expression. Both c-Myc mRNA and protein levels were increased in the transformed clones relative to the parental cells. The transformed clones were not able to grow as tumo rs in vivo when injected into nude or SCID mice. To determine whether the i nvolvement of chromosome 8 in BP-induced mutagenesis was a reproducible eve nt, transformed clones were selected from three additional independently tr eated sets of BP-exposed MCF-10A cultures and analyzed by spectral karyotyp ing (SKY). These transformed sublines also harbored the isochromosome 8q ab normality. Data from this model show that benzo[a]pyrene, a ubiquitous proc arcinogen. can induce selectable morphologic changes in a human mammary epi thelial cell line, and that these transformed cells possess chromosomal abe rrations frequently found in human breast tumors, (C) 2001 Elsevier Science B.V. All rights reserved.