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An analysis for cosegregation of chromosomes and tumorigenicity in 52 hybrids of human diploid × D98AH2 human carcinoma-derived cells reveals the consistent presence of four copies of chromosome 11 in all nontumorigenic hybrids (two from each of the parental cells) and a consistent loss of one or two copies of the 11 in all tumor cells derived from tumorigenic hybrids that grow in nude mice. In our earlier study, assays with restriction fragment length polymorphic (RFLP) markers for the cell parent origin of the chromosomes 11 in the hybrids indicated that at least one of the Nos. 11 lost in the tumor cells is from the diploid. Thus both Nos. 11 of the diploid seem to be required for complete and stable suppression of the tumorigenic phenotype. The results of the present study suggest that chromosome 2 may also carry suppressor information, but this causes only partial suppression of the tumorigenic phenotype in the absence of both Nos. 11. On the other hand, when the hybrids contain full complements of the 2 and the 11, suppression is very stable. All other chromosomes except for Nos. 1, 16, 17, 19, and 21 are clearly discordant with suppression. The latter chromosomes are not discordant often enough to allow their exclusion as possible carriers of suppressor information, particularly in the absence of RFLP evaluations. It is clear, however, that if they do carry such information it is not adequate for maintaining a stably suppressed phenotype in the absence of both Nos. 11 of the diploid.

Tumorigénicity assays of 48 intraspecies hybrids between human carcinoma-derived cells of the D98AH2 (HeLa) cell line and normal human diploid cells revealed that most are nontumorigenic in nude mice. Chromosome analysis revealed that these hybrids contained four chromosomes 11, presumably two from each parental cell. Their tumorigenic segregants sometimes, and their tumors always, had lost one or two copies of chromosome 11 (Klinger and Kaelbling, 1986). In this report we present evidence from analyses of DNA restriction fragment length polymorphic (RFLP) markers for the parental cell origin of the 11 which confirms that the four chromosomes 11 of the nontumorigenic hybrids consisted of two from each cell parent, and most notably, that one No. 11 of the diploid parental cell is always absent in cells of tumors that arise when the tumorigenic hybrids are injected into nude mice. We also found that both Nos. 11 of the D98 cells are identical at many RFLP sites on the short arm suggesting that loss of heterozygosity of the 11, or at least of the short arm of the 11, had occurred. Chromosome 11 of the diploid cells thus appears to carry alleles that suppress the tumorigenic potential of the D98 cells when present in two copies, but not in one. It remains to be seen if other chromosomes of the diploid cell effect suppression in concert with the 11.

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